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Posts Tagged ‘Full genome sequencing’


9:20AM 11/12/2014 – 10th Annual Personalized Medicine Conference at the Harvard Medical School, Boston

REAL TIME Coverage of this Conference by Dr. Aviva Lev-Ari, PhD, RN – Director and Founder of LEADERS in PHARMACEUTICAL BUSINESS INTELLIGENCE, Boston http://pharmaceuticalintelligence.com

9:20 a.m. Panel Discussion – Genomic Technologies

Genomic Technologies

The greatest impetus for personalized medicine is the initial sequencing of the human genome at the beginning of this Century. As we began to recognize the importance of genetic factors in human health and disease, efforts to understand genetic variation and its impact on health have accelerated. It was estimated that it cost more than two billion dollars to sequence the first human genome and reduction in the cost of sequence became an imperative to apply this technology to many facets of risk assessment, diagnosis, prognosis and therapeutic intervention. This panel will take a brief historical look back at how the technologies have evolved over the last 15 years and what the future holds and how these technologies are being applied to patient care.

Genomic Technologies

Opening Speaker and Moderator:

George Church, Ph.D.
Professor of Genetics, Harvard Medical School; Director, Personal Genomics

Genomic Technologies and Sequencing

  • highly predictive, preventative
  • non predictive

Shareable Human Genomes Omics Standards

$800 Human Genome Sequence – Moore’s Law does not account for the rapid decrease in cost of Genome Sequencing

Genome Technologies and Applications

  • Genia nanopore – battery operated device
  • RNA & protein traffic
  • Molecular Stratification Methods – more than one read, sequence ties
  • Brain Atlas  – transcriptome of mouse brains
  • Multigenics – 700 genes: hGH therapies

Therapies

  • vaccine
  • hygiene
  • age

~1970 Gene Therapy in Clinical Trials

Is Omic technologies — a Commodity?

  • Some practices will have protocols
  • other will never become a commodity

 

Panelists:

Sam Hanash, M.D., Ph.D. @MDAndersonNews

Director, Red & Charline McCombs Institute for Early Detection & Treatment of Cancer MD Anderson Cancer Center

Heterogeneity among Cancer cells. Data analysis and interpretation is very difficult, back up technology

Proteins and Peptides before analysis with spectrometry:

  • PM  – Immunotherapy approaches need be combined with other techniques
  • How modification in protein type affects disease
  • amplification of an aberrant protein – when that happens cancer developed. Modeling on a CHip of peptide synthesizer

Mark Stevenson @servingscience

Executive Vice President and President, Life Sciences Solutions
Thermo Fisher Scientific

Issues of a Diagnostics Developer:

  • FDA regulation, need to test on several tissues
  • computational environment
  • PCR, qPCR – cost effective
  • BGI – competitiveness

Robert Green, MD @BrighamWomens

Partners, Health Care Personalized Medicine — >>Disclosure: Illumina and three Pharmas

Innovative Clinical Trial: Alzheimer’s Disease, integration of sequencing with drug development

  • Population based screening with diagnosis
  • Cancer predisposition: Cost, Value, BRCA
  • epigenomics technologies to be integrated
  • Real-time diagnostics
  • Screening makes assumption on Predisposition
  • Public Health view: Phenotypes in the Framingham Studies: 64% pathogenic genes were prevalent – complication based in sequencing.

Questions from the Podium:

  • Variants analysis
  • Metastasis different than solid tumor itself – Genomics will not answer issues related to tumor in special tissues variability

 

 

 

 

– See more at: http://personalizedmedicine.partners.org/Education/Personalized-Medicine-Conference/Program.aspx#sthash.qGbGZXXf.dpuf

@HarvardPMConf

#PMConf

@SachsAssociates

 

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Reporter: Aviva Lev-Ari, PhD, RN

 

Researchers Report on Mutational Patterns in Adenoid Cystic Carcinoma

May 20, 2013

NEW YORK (GenomeWeb News) – A Memorial Sloan-Kettering Cancer Center-led team has taken an exome- and genome-sequencing centered look at the mutations that may be found in the salivary gland cancer adenoid cystic carcinoma, or ACC.

As they reported in Nature Genetics online yesterday, the researchers did exome or genome sequencing on five-dozen matched ACC tumor and normal pairs.

Their analysis unearthed relatively few glitches in each tumor’s protein-coding sequences. But the group found suspicious mutations to several main pathways, including some — such as the PI3-kinase, fibroblast growth factor, and insulin-like growth factor-containing pathway — that may make promising treatment targets.

“Our discovery of genomic alterations in targetable pathways suggests potential avenues for novel treatments to address a typically chemoresistant malignancy,” corresponding author Timothy Chan, an oncology researcher at Memorial Sloan-Kettering, and his colleagues wrote, noting that “[v]erified ACC cell lines are needed to further substantiate the clinical usefulness of the mutations identified here.”

A few genetic glitches have been linked to ACC in the past, the team noted, including a fusion between the transcription factor genes MYB and NFIB. The tumors are also notorious for having higher-than-usual expression of certain genes, such as the epidermal growth factors. Even so, there is still a ways to go in characterizing and treating the aggressive cancer.

To get a better sense of the nature and frequency of mutations involved in ACC, the researchers used Illumina’s HiSeq2000 to do exome sequencing on 55 matched ACC and normal samples, as well as whole-genome sequencing on five more tumor-normal pairs.

For the exome sequencing experiments, they used Agilent SureSelect kits to capture protein-coding portions of the genome prior to sequencing. In the subsequent analyses, meanwhile, the group relied on Life Tehnologies’ SOLiD and Illumina’s MiSeq platforms to verify apparent single nucleotide glitches and small insertions and deletions.

With 106-fold coverage of the exomes, on average, and 37-fold average coverage of the genomes, the group was able to track down a mean of almost two-dozen somatic coding alterations per tumor.

When they used an algorithm called CHASM to distinguish between driver and passenger mutations in a set of 710 validated non-synonymous mutations, the researchers saw an over-representation of apparent driver mutations affecting genes known for processes ranging from chromatin regulation and DNA damage response to signaling and metabolism.

For instance, more than one-third of the tumors harbored mutations to chromatin regulators or chromatin state modifying genes such as SMARCA2, CREBBP, and KDM6A. Similarly, the researchers tracked down multiple mutations to genes coding for enzymes involved in adding or removing methylation and acetylation marks to histones.

Glitches to DNA damage response pathways also turned up in multiple tumors, they reported, as did mutations involving genes from the FGF-IGF-PI3K and other signaling pathways.

Some 57 percent of the tumors tested contained the MYB-NFIB fusion that had been implicated in ACC previously. But the new analysis also turned up mutations affecting genes that interact with MYB and in the NFIB gene itself, pointing to widespread — and perhaps complex — involvement for the two transcription factors in ACC.

“Our data highlight MYB as an active oncogenic partner in fusion transcripts in ACC,” the study’s authors said, “but also suggest a separate role for NFIB, given the presence of mutations specific to this gene.”

Going forward, the group hopes to see further analyses on alterations uncovered in the current study, particularly those falling in pathways that might be prone to clinical interventions.

“[O]ur data provide insights into the genetic framework underlying ACC oncogenesis,” the researchers concluded, “and establish a foundation for identifying new therapeutic strategies.”

 

 

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Finding the Genetic Links in Common Disease:  Caveats of Whole Genome Sequencing Studies

Writer and Reporter: Stephen J. Williams, Ph.D.

In the November 23, 2012 issue of Science, Jocelyn Kaiser reports (Genetic Influences On Disease Remain Hidden in News and Analysis)[1] on the difficulties that many genomic studies are encountering correlating genetic variants to high risk of type 2 diabetes and heart disease.  At the recent American Society of Human Genetics annual 2012 meeting, results of several DNA sequencing studies reported difficulties in finding genetic variants and links to high risk type 2 diabetes and heart disease.  These studies were a part of an international effort to determine the multiple genetic events contributing to complex, common diseases like diabetes.  Unlike Mendelian inherited diseases (like ataxia telangiectasia) which are characterized by defects mainly in one gene, finding genetic links to more complex diseases may pose a problem as outlined in the article:

  • Variants may be so rare that massive number of patient’s genome would need to be analyzed
  • For most diseases, individual SNPs (single nucleotide polymorphisms) raise risk modestly
  • Hard to find isolated families (hemophilia) or isolated populations (Ashkenazi Jew)
  • Disease-influencing genes have not been weeded out by natural selection after human population explosion (~5000 years ago) resulted in numerous gene variants
  • What percentage variants account for disease heritability (studies have shown this is as low as 26% for diabetes with the remaining risk determined by environment)

Although many genome-wide-associations studies have found SNPs that have causality to increasing risk diseases such as cancer, diabetes, and heart disease, most individual SNPs for common diseases raise risk by about only 20-40% and would be useless for predicting an individual’s chance they will develop disease and be a candidate for a personalized therapy approach.  Therefore, for common diseases, investigators are relying on direct exome sequencing and whole-genome sequencing to detect these medium-rare risk variants, rather than relying on genome-wide association studies (which are usually fine for detecting the higher frequency variants associated with common diseases).

Three of the many projects (one for heart risk and two for diabetes risk) are highlighted in the article:

1.  National Heart, Lung and Blood Institute Exome Sequencing Project (ESP)[2]: heart, lung, blood

  • Sequenced 6,700 exomes of European or African descent
  • Majority of variants linked to disease too rare (as low as one variant)
  • Groups of variants in the same gene confirmed link between APOC3 and higher risk for early-onset heart attack
  • No other significant gene variants linked with heart disease

2.  T2D-GENES Consortium: diabetes

Sequenced 5,300 exomes of type 2 diabetes patients and controls from five ancestry groups
SNP in PAX4 gene associated with disease in East Asians
No low-frequency variant with large effect though

3.  GoT2D: diabetes

  • After sequencing 2700 patient’s exomes and whole genome no new rare variants above 1.5% frequency with a strong effect on diabetes risk

A nice article by Dr. Sowmiya Moorthie entitled Involvement of rare variants in common disease can be found at the PGH Foundation site http://www.phgfoundation.org/news/5164/ further discusses this conundrum,  and is summarized below:

“Although GWAs have identified many SNPs associated with common disease, they have as yet had little success in identifying the causative genetic variants. Those that have been identified have only a weak effect on disease risk, and therefore only explain a small proportion of the heritable, genetic component of susceptibility to that disease. This has led to the common disease-common variant hypothesis, which predicts that common disease-causing genetic variants exist in all human populations, but each individual variant will necessarily only have a small effect on disease susceptibility (i.e. a low associated relative risk).

An alternative hypothesis is the common disease, many rare variants hypothesis, which postulates that disease is caused by multiple strong-effect variants, each of which is only found in a few individuals. Dickson et al. in a paper in PLoS Biology postulate that these rare variants can be indirectly associated with common variants; they call these synthetic associations and demonstrate how further investigation could help explain findings from GWA studies [Dickson et al. (2010) PLoS Biol. 8(1):e1000294][3].  In simulation experiments, 30% of synthetic associations were caused by the presence of rare causative variants and furthermore, the strength of the association with common variants also increased if the number of rare causative variants increased. “

one_of_many rare variants

Figure from Dr. Moorthie’s article showing the problem of “finding one in many”.

(please   click to enlarge)

Indeed, other examples of such issues concerning gene variant association studies occur with other common diseases such as neurologic diseases and obesity, where it has been difficult to clearly and definitively associate any variant with prediction of risk.

For example, Nuytemans et. al.[4] used exome sequencing to find variants in the vascular protein sorting 3J (VPS35) and eukaryotic transcription initiation factor 4  gamma1 (EIF4G1) genes, tow genes causally linked to Parkinson’s Disease (PD).  Although they identified novel VPS35 variants none of these variants could be correlated to higher risk of PD.   One EIF4G1 variant seemed to be a strong Parkinson’s Disease risk factor however there was “no evidence for an overall contribution of genetic variability in VPS35 or EIF4G1 to PD development”.

These negative results may have relevance as companies such as 23andme (www.23andme.com) claim to be able to test for Parkinson’s predisposition.  To see a description of the LLRK2 mutational analysis which they use to determine risk for the disease please see the following link: https://www.23andme.com/health/Parkinsons-Disease/. This company and other like it have been subjects of posts on this site (Personalized Medicine: Clinical Aspiration of Microarrays)

However there seems to be more luck with strategies focused on analyzing intronic sequence rather than exome sequence. Jocelyn Kaiser’s Science article notes this in a brief interview with Harry Dietz of Johns Hopkins University where he suspects that “much of the missing heritability lies in gene-gene interactions”.  Oliver Harismendy and Kelly Frazer and colleagues’ recent publication in Genome Biology  http://genomebiology.com/content/11/11/R118 support this notion[5].  The authors used targeted resequencing of two endocannabinoid metabolic enzyme genes (fatty-acid-amide hydrolase (FAAH) and monoglyceride lipase (MGLL) in 147 normal weight and 142 extremely obese patients.

These patients were enrolled in the CRESCENDO trial and patients analyzed were of European descent. However, instead of just exome sequencing, the group resequenced exome AND intronic sequence, especially focusing on promoter regions.   They identified 1,448 single nucleotide variants but using a statistical filter (called RareCover which is referred to as a collapsing method) they found 4 variants in the promoters and intronic areas of the FAAH and MGLL genes which correlated to body mass index.  It should be noted that anandamide, a substrate for FAAH, is elevated in obese patients. The authors did note some issues though mentioning that “some other loci, more weakly or inconsistently associated in the original GWASs, were not replicated in our samples, which is not too surprising given the sample size of our cohort is inadequate to replicate modest associations”.

PLEASE WATCH VIDEO on the National Heart, Lung and Blood Institute Exome Sequencing Project

https://www.youtube.com/watch?v=-Qr5ahk1HEI

REFERENCES

http://www.phgfoundation.org/news/5164/  PHG Foundation

1.            Kaiser J: Human genetics. Genetic influences on disease remain hidden. Science 2012, 338(6110):1016-1017.

2.            Tennessen JA, Bigham AW, O’Connor TD, Fu W, Kenny EE, Gravel S, McGee S, Do R, Liu X, Jun G et al: Evolution and functional impact of rare coding variation from deep sequencing of human exomes. Science 2012, 337(6090):64-69.

3.            Dickson SP, Wang K, Krantz I, Hakonarson H, Goldstein DB: Rare variants create synthetic genome-wide associations. PLoS biology 2010, 8(1):e1000294.

4.            Nuytemans K, Bademci G, Inchausti V, Dressen A, Kinnamon DD, Mehta A, Wang L, Zuchner S, Beecham GW, Martin ER et al: Whole exome sequencing of rare variants in EIF4G1 and VPS35 in Parkinson disease. Neurology 2013, 80(11):982-989.

5.            Harismendy O, Bansal V, Bhatia G, Nakano M, Scott M, Wang X, Dib C, Turlotte E, Sipe JC, Murray SS et al: Population sequencing of two endocannabinoid metabolic genes identifies rare and common regulatory variants associated with extreme obesity and metabolite level. Genome biology 2010, 11(11):R118.

Other posts on this site related to Genomics include:

Cancer Biology and Genomics for Disease Diagnosis

Diagnosis of Cardiovascular Disease, Treatment and Prevention: Current & Predicted Cost of Care and the Promise of Individualized Medicine Using Clinical Decision Support Systems

Ethical Concerns in Personalized Medicine: BRCA1/2 Testing in Minors and Communication of Breast Cancer Risk

Genomics & Genetics of Cardiovascular Disease Diagnoses: A Literature Survey of AHA’s Circulation Cardiovascular Genetics, 3/2010 – 3/2013

Genomics-based cure for diabetes on-the-way

Personalized Medicine: Clinical Aspiration of Microarrays

Late Onset of Alzheimer’s Disease and One-carbon Metabolism

Genetics of Disease: More Complex is How to Creating New Drugs

Genetics of Conduction Disease: Atrioventricular (AV) Conduction Disease (block): Gene Mutations – Transcription, Excitability, and Energy Homeostasis

Centers of Excellence in Genomic Sciences (CEGS): NHGRI to Fund New CEGS on the Brain: Mental Disorders and the Nervous System

Cancer Genomic Precision Therapy: Digitized Tumor’s Genome (WGSA) Compared with Genome-native Germ Line: Flash-frozen specimen and Formalin-fixed paraffin-embedded Specimen Needed

Mitochondrial Metabolism and Cardiac Function

Pancreatic Cancer: Genetics, Genomics and Immunotherapy

Issues in Personalized Medicine in Cancer: Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing

Quantum Biology And Computational Medicine

Personalized Cardiovascular Genetic Medicine at Partners HealthCare and Harvard Medical School

Centers of Excellence in Genomic Sciences (CEGS): NHGRI to Fund New CEGS on the Brain: Mental Disorders and the Nervous System

LEADERS in Genome Sequencing of Genetic Mutations for Therapeutic Drug Selection in Cancer Personalized Treatment: Part 2

Consumer Market for Personal DNA Sequencing: Part 4

Personalized Medicine: An Institute Profile – Coriell Institute for Medical Research: Part 3

Whole-Genome Sequencing Data will be Stored in Coriell’s Spin off For-Profit Entity

 

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Malaria Genomes

 

Curator: Larry H Bernstein, MD, FCAP

 

 Five Malaria Genomes Sequenced

Zimmerman et al.
Whole Genome Sequencing of Field Isolates Provides Robust Characterization of Genetic Diversity in Plasmodium vivax.
Scientists have sequenced the entire genomes of five Plasmodium vivax strains taken from the blood of patients on different continents, providing
  • a wealth of new data to help in the future mapping of malarial parasite traits such as
  • drug resistance, and
determine how different strains are geographically distributed.
  • identified over 80,000 SNPs that can form the basis of association studies and
  • population surveys to study the diversity of P. vivax in a single region.
Malaria.

Malaria. (Photo credit: maestro garabito/escuela potosina)

Malaria distribution map. Most countries with ...

Malaria distribution map. Most countries with a high distribution of malaria also have a high distribution of parasitic worm infections. (Photo credit: Wikipedia)

English: This thin film Giemsa stained microgr...

English: This thin film Giemsa stained micrograph reveals a mature Plasmodium vivax trophozoite. P. vivax trophozoites show amoeboid cytoplasm, large chromatin dots, and fine, yellowish-brown pigment. RBCs are enlarged 1 1/2 – 2X, and may be distorted. If visible, Schüffner’s dots may appear finer than those seen in P. vivax. (Photo credit: Wikipedia)

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Genome Sequencing of the Healthy

Curators: Larry H. Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN

 

Key Issues in Genome Sequencing of Healthy Individuals
Eric Topol, MD, Genomic Medicine

I briefly review 3 important articles that recently appeared, each touching on important controversies in the use of whole genome sequencing
http://www.linkedin.com/…/Key-Issues-in-Genome-Sequencing-218

http://boards.medscape.com/.2a38676f!comment=1

I briefly review 3 important articles that recently appeared, each touching on important controversies in the use of whole genome sequencing:
1. Should Healthy People Have Their Genomes Sequenced At This Time? Wall Street Journal, February 15, 2013.
2. A Genetic Code for Genius? Wall Street Journal, February 15, 2013.
3. Francke U, Djamco C, Kiefer AK, et al. Dealing with the unexpected: consumer responses to direct-access BRCA mutation testing. PeerJ. 2012;1:e8. DOI 10.7717/peerj.8
Welcome to another segment on genomic medicine. Today, I want to get into 3 different articles: 2 from the Wall Street (“Medical”) Journal and the other from a new open access journal, PeerJ. All of them are related to the issues of genome sequencing.
First, there was a debate about whether all healthy people should have their genomes sequenced. It was a debate between Atul Butte from Stanford and Robert Green from Harvard. In this debate, they made a number of really good points, and I have linked you to that article if you’re interested.
Basically, is it too early to get sequencing because we need millions of people to have whole genome sequencing who are healthy in order for that information to be truly informative. The price continues to drop. So even though the sequencing that is done today would still be valid if it’s done accurately, the problem we have, of course, is a lack of enough people who are phenotyped with a particular condition to extract all the best information that is truly informative from whole genome sequencing.
 it’s unlikely that even 2000 individuals with high IQ will be particularly informative but also, of course, what this could do from a bioethical standpoint. I’ll leave that to your imagination and thoughts as to where this could go – that is, trying to understand, even with limited power, the genomics of intelligence.
The third article, which is also very interesting, comes from this new journal called PeerJ. I’m on the editorial board of that journal, and I think it’s terrific to see open access, high-quality biomedical articles.
This one comes from the company 23andMe. From a very large number of individuals – now over 200,000 and rapidly approaching 1 million – who have had genome scans, a large number of women had information about the BRCA gene and whether they had a significant mutation. From these women who volunteered to participate in this study, we learned that they had no serious psychological repercussions from knowledge of this highly actionable BRCA pathogenic mutation.
This goes along with the previous study that we had done at Scripps led by my colleague Cinnamon Bloss in the New England Journal of Medicine, where, in thousands of individuals who had genome scans and had such data as ApoE4 status known to them for the first time, there were no significant negative psychological repercussions.

Should Healthy People Have Their Genomes Sequenced At This Time?

‘Patients in Waiting’

Injecting so much uncertain genetic information into the doctor-patient relationship could create legions of “patients in waiting” leading to unnecessary tests, harmful outcomes and lifelong anxiety. As private software companies compete to provide more genomic “findings” to a medical culture that is trained to search for diagnostic fire when they smell the smoke of disease risk, there are potential benefits. But there is also a real possibility that medical resources will be squandered and patients could be harmed.

Perhaps we all underestimated how complicated it would be to move genomic knowledge into the practice of medicine and public health. Now is the time to make sure we get this right through rigorous basic and clinical studies that define which mutations are dangerous, and distinguish useful from unnecessary interventions. Soon, genomic insights will give us early warnings about life-threatening illnesses that we may be able to prevent. Soon, standards will be available to guide doctors about which findings are meaningful and which are not.

Soon, there may be evidence to support the benefits of screening healthy individuals. But not today.

SOURCE:
Table 1. Performance values for genome sequenc...

Table 1. Performance values for genome sequencing technologies including Sanger methods and Massively Parallel Seqeuncing methods. Sinville, R. and Soper, S. A. High resolution DNA separations using microchip electrophoresis. J. Sep. Sci. 2007, 30, 1714 – 1728 Morozova,O. and Marra, M. A. Applications of next-generation sequencing technologies in functional genomics. Genomics. 92 (2008) 255–264 (Photo credit: Wikipedia)

 

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Reporter: Aviva Lev-Ari, PhD, RN

Inaugural Genomics in Medicine

Individualized Care for Improved Outcomes

February 11-12

Moscone North Convention Center • San Francisco, CA

Organized by

Cambridge Healthtech Institute

Monday, February 11

7:30 am Registration and Morning Coffee

8:25 Chairperson’s Opening Remarks

Screening for Rare and

Difficult to Diagnose Diseases

8:30 KEYNOTE PRESENTATION:

Genomically-Supported Diagnostic and

Drug Reposition Strategies out

of Academia

Hakon Hakonarson, M.D., Ph.D., Director, Center for Applied

Genomics, Children’s Hospital of Philadelphia

This talk will discuss genomic strategies applied in academia

to identify subsets of patients who, based on their genetic

make-up, are predicted to have a favorable response profile to

drugs that come from reposition opportunities.

9:00 Evolving Approaches to Mutation Detection in

Rare Diseases

Tom Scholl, Vice President, Research & Development,

Integrated Genetics, LabCorp

Emerging trends in this field that include the expansion of

content in clinical tests to include many loci and increased

clinical sensitivity by expanding numbers of mutations detected

or whole gene sequencing will be presented.

9:30 From Raw Sequencing Data to

Functional Interpretation

Daniel MacArthur, Ph.D., Group Leader, Analytic and

Translational Genetics Unit, Massachusetts General Hospital

This presentation will discuss the key lessons learned

from large-scale sequencing studies in both common and

rare diseases with a particular focus on finding mutations

underlying severe muscle diseases.

10:00 Coffee Break with Exhibit and Poster Viewing

10:30 Providing Whole Genome Sequencing in the Clinic

David Dimmock, M.D., Assistant Professor, Pediatrics,

Medical College of Wisconsin

This presentation will focus on advances in the implementation

of genome wide sequencing in clinical practice. It will address

counseling and consent issues specific to testing children.

Specifically, it will highlight the challenges of execution in the

acute care setting.

11:00 Clinical Utility of Whole Exome Sequencing

Christine M. Eng, M.D., Professor, Department of Molecular

and Human Genetics, Baylor College of Medicine

This presentation will discuss the role of whole exome

sequencing in the diagnostic evaluation of patients with

challenging phenotypes of genetic etiology. Examples of

clinical utility, directed medical care, and cost-effectiveness

of the whole exome approach to clinical diagnostics will be

presented.

11:30 A Neuronal Carnitine Deficiency Hypothesis

for Autism

Arthur L. Beaudet, M.D., Henry and Emma Meyer Professor

and Chair, Department of Molecular and Human Genetics,

Baylor College of Medicine

We have published a paper entitled “A common X-linked

inborn error of carnitine biosynthesis may be a risk factor for

nondysmorphic autism” (PMID: 22566635). We propose a

neuronal carnitine deficiency hypothesis as one risk factor

or cause for autism whereby 10-20% of autism might

be preventable.

12:00 pm Luncheon Presentation

(Sponsorship Opportunity Available) or Lunch on

Your Own

Predictive Tests for

Improved Patient Outcomes

1:25 Chairperson’s Remarks

1:30 Implementation of Personalized Healthcare into

Clinical Practice: Lessons Learned

Kathryn Teng, M.D., FACP, Director, Center for Personalized

Healthcare, Cleveland Clinic

Integrating a pharmacogenetics program into clinical practice

requires a vision for the future of healthcare and a roadmap to

reach that vision. Pioneering the road to achieving this vision

has brought challenges and has allowed for the creation of

solutions that might be applied universally.

2:00 Molecular Profiling of Tumors to Select Therapy

in Patients with Advanced Refractory Tumors

Ramesh Ramanathan, M.D., Medical Director, The Virginia

G. Piper Cancer Center Clinical Trials

This presentation will discuss molecular profiling of tumors

using IHC, CGH and whole genome/exome sequencing of

tumors to find actionable targets for therapy. Clinical trials

and case reports of patients treated by this approach will

be presented.

2:30 Sponsored Presentations (Opportunities Available)

3:00 Refreshment Break with Exhibit and

Poster Viewing

3:30 Gene Panels vs. Whole Exome Sequencing in

Cancer Molecular Testing

Madhuri Hegde, Ph.D., FACMG, Associate Professor, Senior

Director, Emory Genetics Laboratory, Department of Human

Genetics, Emory University School of Medicine

TriConference.com 5

Individualized Care for Improved Outcomes

4:00 Next Generation Sequencing and

Cancer Diagnostics

Phil Stephens, Ph.D., Vice President, Cancer Genomics,

Foundation Medicine

Foundation Medicine has developed FoundationOne™, a

CLIA-certified, comprehensive cancer genomic test that

analyzes routine clinical specimens for somatic alterations in

189 relevant cancer genes. Experience with the initial 1,000

consecutive patients will be presented.

4:30 KEYNOTE PRESENTATION:

Clinical Cancer Genotyping – Snapshot

John Iafrate, M.D., Ph.D., Assistant Professor,

Pathology, Harvard Medical School; Assistant

Pathologist, Massachusetts General Hospital

The challenges and opportunities of implementing a broad

genotyping assay in routine clinical management of cancer

patients will be discussed. Snapshot was launched over 3

years ago at the Massachusetts General Hospital, with the

goal of providing all cancer patients with a genetic fingerprint

to guide therapeutic decisions. Lessons learned will be

outlined, and a roadmap to effectively move testing forward

into the Next Gen sequencing era.

5:00 Breakout Discussions (See Web for Details)

6:00 Close of Day

Tuesday, February 12

8:00 am Morning Coffee

Data Management and Analysis

8:10 Chairperson’s Remarks

8:15 Under the Hood of the 1000 Genomes Project

Mark A. DePristo, Ph.D., Associate Director, Medical

and Population Genetics Analysis, Broad Institute of MIT

and Harvard (on behalf of The 1000 Genomes Project

Consortium)

This presentation discusses the evolution of the nextgeneration

sequencing (NGS) data underlying the public

1000 Genomes Project resource, from some of the earliest

technologies of 2009 to today’s state-of-the-art data. It

will also highlight key NGS analytic advances originating

from the Project.

8:45 Delivering Genomic Medicine: Challenges

and Opportunities

Heidi L. Rehm, Ph.D., FACMG, Assistant Professor,

Pathology, BWH and Harvard Medical School; Director,

Laboratory for Molecular Medicine, Partners Healthcare

Center for Personalized Genetic Medicine

This talk will cover the speaker’s experience in offering clinical

sequencing to patients, from disease-targeted panels to whole

genome analyses as well as supporting the interpretation

and delivery of those results to physicians. It will also cover

approaches to data sharing within the community.

9:15 From Sequence Files to

Sponsored by

Physicians Report and the Tools

Needed to Get There

Martin Seifert, Ph.D., CEO,

Genomatix Software

Providing actionable biology from NGS data in a report useful

to the practicing clinician is difficult. Ensuring the report is

accurate, reproducible, and reflects the biology of the patient

is an even larger task. We will show examples of Genomatix’

approach to these issues and how we successfully ensure a

secure, accurate, and reproducible report, bridging the gap

from sequencer to clinician.

9:30 Rapid Identification of

Sponsored by

Disease Causative Mutations

Ali Torkamani, Ph.D., Co-Founder & CSO,

Cypher Genomics

Recent successes in clinical genome sequencing have

highlighted the potential for sequencing to greatly improve

molecular diagnosis and clinical decision-making. However,

these successes have relied upon large bioinformatics teams

and in-depth literature surveys. We will demonstrate how the

Cypher Genomics software service can quickly return a small

set of well-annotated genetic variants most likely to contribute

to a patient’s disease.

10:00 Coffee Break with Exhibit and

Poster Viewing

Getting Genomic Testing to Clinic

10:30 Sequence Data on Demand: Access,

Visualization and Communication of Genome

Sequence Data between Physicians, Researchers,

and Patients

Sitharthan Kamalakaran, Ph.D., Senior Member, Research

Staff, Philips Research North America

Patients’ genome sequences are informative for clinical care

over the patient’s lifetime and not just for the diagnosis at

hand. We present a web-accessible interface for clinicians to

integrate relevant patient genome data in their routine practice

through clinically-framed queries.

11:00 Targeted Next Generation Sponsored by

Sequencing in FFPE Tumor Samples:

Distilling High Quality Information from Low

Quality Samples

Sachin Sah, Senior Scientist, Diagnostics Research

Development, Asuragen, Inc.

SuraSeq™ PCR-based enrichment procedures enable accurate

and sensitive mutation detection from nanogram inputs of

challenging FFPE tumor DNA. Case studies will be presented

that highlight the use of complementary NGS platforms and

novel bioinformatics for discovery and confirmation studies.

11:30 Transitioning New Technologies from the Bench to the Bedside: Direct Fetal Testing Using Circulating

Cell-Free DNA

Allan T. Bombard, M.D., CMO, Sequenom

This presentation will address clinical test implementation of new tests in the US, using circulating

cell-free DNA for noninvasive

prenatal testing (NIPT) of fetal aneuploidy from maternal plasma as an example.

12:00 Moving Genomic Screening to the Clinic: Next Steps

Bruce R. Korf, M.D., Ph.D., Wayne H. and Sara Crews Finley Chair in Medical Genetics; Professor and Chair,

Department of Genetics; Director, Heflin Center for Genomic Sciences, University of Alabama at Birmingham

Since the sequencing of the human genome there has been an expectation that a flood of advances would find their

way to the clinic, and, indeed, the pace of translation of genomics to clinical application is accelerating. It is likely that the future of

medical care will evolve by the convergence of two disruptive technologies – that of information science and genomics, which, in a

sense can be viewed as one and the same.

12:30 pm Close of Symposium

Featured Presentations

Genomically-Supported Diagnostic and

Drug Reposition Strategies out of Academia

Hakon Hakonarson, M.D., Ph.D., Director, Center

for Applied Genomics, Children’s Hospital of

Philadelphia

Clinical Cancer Genotyping – Snapshot

John Iafrate, M.D., Ph.D., Assistant Professor,

Pathology, Harvard Medical School; Assistant

Pathologist, Massachusetts General Hospital

Moving Genomic Screening to the Clinic:

Next Steps

Bruce R. Korf, M.D., Ph.D., Wayne H. and Sara

Crews Finley Chair in Medical Genetics;

Professor and Chair, Department of Genetics;

Director, Heflin Center for Genomic Sciences,

University of Alabama at Birmingham

Reasons to Attend

• Hear keynote presentations from Dr. Hakon

Hakonarson of CHOP and Dr. John Iafrate of MGH

• Find out how to transition genomic

screening to the clinic

• Discover evolving approaches to

mutation detection

• Explore data management and analysis solutions

• Learn the role of pharmacogenomics in

patient care

• Network with genomic thought leaders

• Par ticipate in interactive, problem-solving

breakout discussions

TriConference.com

February 11-15 • Moscone North Convention Center • San Francisco, CA

2013

Molecular Med

Tri-Con

Premier Sponsors:

2 Genomics in Medicine

Plenary Keynotes 2013 Sponsors

Wednesday, February 13 8:00 – 9:40 am

Personalized Oncology – Fulfilling the Promise for

Today’s Patients

In honor of the 20th anniversary of the Molecular Medicine Tri-conference, CHI and

Cancer Commons will present a plenary panel on Personalized Oncology. Innovations

such as NGS and The Cancer Genome Atlas have revealed that cancer comprises

hundreds of distinct molecular diseases. Early clinical successes with targeted

therapies suggest that cancer might one day be managed as a chronic disease using

an evolving cocktail of drugs. Representing all five conference channels, Diagnostics,

Therapeutics, Clinical, Informatics, and Cancer, a panel of experts will lead a highly

interactive exploration of what it will take to realize this vision in the near future.

Moderator: Marty Tenenbaum, Ph.D., Founder and Chairman, Cancer

Commons; Prominent AI Researcher; Cancer Survivor

Tony Blau, M.D., Professor, Department of Medicine/Hematology and

Adjunct Professor, Department of Genome Sciences, University of

Washington; Attending Physician, Seattle Cancer Care Alliance; Co-

Director, Institute for Stem Cell and Regenerative Medicine, University of

Washington and the Program for Stem and Progenitor Cell Biology at the

UW/FHCRC Cancer Consortium; Founder and Scientific Officer, Partners

in Personal Oncology

Sarah Greene, Executive Director, Cancer Commons

Laurence Marton, M.D., Adjunct Professor, Department of Laboratory

Medicine, University of California San Francisco; former Dean of

Medicine, University of Wisconsin

Jane Reese-Coulbourne, MS, ChE, Executive Director, Reagan-Udall

Foundation for the FDA; former Board Chair, Lung Cancer Alliance;

Cancer Survivor

Anil Sethi, CEO, Pinch Bio; HL7 Pioneer and Health Informatics

Entrepreneur

Joshua Stuart, Ph.D., Associate Professor, Department of Biomolecular

Engineering, University of California Santa Cruz

Thursday, February 14 8:00 – 9:40 am

Plenary Keynote Panel: Emerging Technologies &

Industry Perspectives

This session features a series of presentations on emerging and hot technologies in

diagnostics, drug discovery & development, informatics, and oncology. Interactive

Q&A discussion with the audience will be included.

Moderator: To be Announced

Gregory Parekh, Ph.D., CEO, Biocartis

Kevin Bobofchak, Ph.D., Pathway Studio Product Manager, Elsevier

Jeremy Bridge-Cook, Ph.D., Senior Vice President, Research &

Development, Luminex Corporation

Panelist to be Announced, Remedy Informatics

Harry Glorikian, Managing Partner, Scientia Advisors, LLC

Lynn R. Zieske, Ph.D., Vice President, Commercial Solutions, Singulex, Inc.

Sponsored by

Premier Sponsors:

Corporate Sponsors:

Molecular

Corporate Support Sponsors:

TriConference.com 3

Conference Programs:

Feb 13-15

Diagnostics Channel

Molecular Diagnostics

Personalized Diagnostics

Cancer Molecular Markers

Circulating Tumor Cells

Digital Pathology – NEW

Companion Diagnostics – NEW

Therapeutics Channel

Mastering Medicinal Chemistry

Cancer Biologics

Clinical and Translational Science

Clinical Channel

Oncology Clinical Trials

Clinical and Translational Science

Clinical Sequencing – NEW

Informatics Channel

Bioinformatics in the Genome Era

Integrated R&D Informatics and Knowledge Management

Cancer Channel

Cancer Molecular Markers

Circulating Tumor Cells

Predictive Pre-Clinical Models in Oncology – NEW

Oncology Clinical Trials

Cancer Biologics

Symposia*:

Feb 11-12

Targeting Cancer Stem Cells

Genomics in Medicine – NEW

Point-of-Care Diagnostics

Quantitative Real-Time PCR – NEW

Next Generation Pathology

Partnering Forum*:

Feb 11-12

Emerging Molecular Diagnostics

Short Courses*:

Feb 12

1:30-4:30pm

SC1 Identification & Characterization of Cancer Stem Cells

SC2 Commercialization Boot Camp: Manual for Success in

the Molecular Diagnostics Marketplace

SC3 NGS Data and the Cloud

SC4 Best Practices in Personalized and Translational

Medicine

SC5 Latest Advances in Molecular Pathology

SC6 Regulatory Approval of a Therapeutic & Companion

Diagnostic: Nuts & Bolts

SC7 PCR Part I: qPCR in Molecular Diagnostics

SC8 Data Visualization

SC9 Methods for Synthesis & Screening of Macrocyclic

Compound Libraries

5:00-8:00pm (Dinner)

SC10 PCR Part II: Digital PCR Applications and Advances

SC11 Sample Prep and Biorepositories for Cancer Research

SC12 Next-Generation Sequencing in Molecular Pathology:

Challenges and Applications

SC13 Strategies for Companion Diagnostics Development

SC14 Patient-Derived Cancer Tissue Xenograph Models

SC16 Microfluidics Technology and Market Trends

SC17 Open Cloud & Data Science

Get the best 5-day value! Our All Access

Packages is a convenient, cost-effective way

to attend each aspect of Molecular Med

TRI-CON 2013. Package includes access to

1 Symposium or Partnering Forum, 2 Short

Courses and 1 Conference Program.

TRI-CON All Access Package

*Separate reg required with a la carte pricing

Co-located Event

4 Genomics in Medicine

Inaugural Genomics in Medicine

Monday, February 11

7:30 am Registration and Morning Coffee

8:25 Chairperson’s Opening Remarks

Screening for Rare and

Difficult to Diagnose Diseases

8:30 KEYNOTE PRESENTATION:

Genomically-Supported Diagnostic and

Drug Reposition Strategies out

of Academia

Hakon Hakonarson, M.D., Ph.D., Director, Center for Applied

Genomics, Children’s Hospital of Philadelphia

This talk will discuss genomic strategies applied in academia

to identify subsets of patients who, based on their genetic

make-up, are predicted to have a favorable response profile to

drugs that come from reposition opportunities.

9:00 Evolving Approaches to Mutation Detection in

Rare Diseases

Tom Scholl, Vice President, Research & Development,

Integrated Genetics, LabCorp

Emerging trends in this field that include the expansion of

content in clinical tests to include many loci and increased

clinical sensitivity by expanding numbers of mutations detected

or whole gene sequencing will be presented.

9:30 From Raw Sequencing Data to

Functional Interpretation

Daniel MacArthur, Ph.D., Group Leader, Analytic and

Translational Genetics Unit, Massachusetts General Hospital

This presentation will discuss the key lessons learned

from large-scale sequencing studies in both common and

rare diseases with a particular focus on finding mutations

underlying severe muscle diseases.

10:00 Coffee Break with Exhibit and Poster Viewing

10:30 Providing Whole Genome Sequencing in the Clinic

David Dimmock, M.D., Assistant Professor, Pediatrics,

Medical College of Wisconsin

This presentation will focus on advances in the implementation

of genome wide sequencing in clinical practice. It will address

counseling and consent issues specific to testing children.

Specifically, it will highlight the challenges of execution in the

acute care setting.

11:00 Clinical Utility of Whole Exome Sequencing

Christine M. Eng, M.D., Professor, Department of Molecular

and Human Genetics, Baylor College of Medicine

This presentation will discuss the role of whole exome

sequencing in the diagnostic evaluation of patients with

challenging phenotypes of genetic etiology. Examples of

clinical utility, directed medical care, and cost-effectiveness

of the whole exome approach to clinical diagnostics will be

presented.

11:30 A Neuronal Carnitine Deficiency Hypothesis

for Autism

Arthur L. Beaudet, M.D., Henry and Emma Meyer Professor

and Chair, Department of Molecular and Human Genetics,

Baylor College of Medicine

We have published a paper entitled “A common X-linked

inborn error of carnitine biosynthesis may be a risk factor for

nondysmorphic autism” (PMID: 22566635). We propose a

neuronal carnitine deficiency hypothesis as one risk factor

or cause for autism whereby 10-20% of autism might

be preventable.

12:00 pm Luncheon Presentation

(Sponsorship Opportunity Available) or Lunch on

Your Own

Predictive Tests for

Improved Patient Outcomes

1:25 Chairperson’s Remarks

1:30 Implementation of Personalized Healthcare into

Clinical Practice: Lessons Learned

Kathryn Teng, M.D., FACP, Director, Center for Personalized

Healthcare, Cleveland Clinic

Integrating a pharmacogenetics program into clinical practice

requires a vision for the future of healthcare and a roadmap to

reach that vision. Pioneering the road to achieving this vision

has brought challenges and has allowed for the creation of

solutions that might be applied universally.

2:00 Molecular Profiling of Tumors to Select Therapy

in Patients with Advanced Refractory Tumors

Ramesh Ramanathan, M.D., Medical Director, The Virginia

G. Piper Cancer Center Clinical Trials

This presentation will discuss molecular profiling of tumors

using IHC, CGH and whole genome/exome sequencing of

tumors to find actionable targets for therapy. Clinical trials

and case reports of patients treated by this approach will

be presented.

2:30 Sponsored Presentations (Opportunities Available)

3:00 Refreshment Break with Exhibit and

Poster Viewing

3:30 Gene Panels vs. Whole Exome Sequencing in

Cancer Molecular Testing

Madhuri Hegde, Ph.D., FACMG, Associate Professor, Senior

Director, Emory Genetics Laboratory, Department of Human

Genetics, Emory University School of Medicine

TriConference.com 5

Individualized Care for Improved Outcomes

4:00 Next Generation Sequencing and

Cancer Diagnostics

Phil Stephens, Ph.D., Vice President, Cancer Genomics,

Foundation Medicine

Foundation Medicine has developed FoundationOne™, a

CLIA-certified, comprehensive cancer genomic test that

analyzes routine clinical specimens for somatic alterations in

189 relevant cancer genes. Experience with the initial 1,000

consecutive patients will be presented.

4:30 KEYNOTE PRESENTATION:

Clinical Cancer Genotyping – Snapshot

John Iafrate, M.D., Ph.D., Assistant Professor,

Pathology, Harvard Medical School; Assistant

Pathologist, Massachusetts General Hospital

The challenges and opportunities of implementing a broad

genotyping assay in routine clinical management of cancer

patients will be discussed. Snapshot was launched over 3

years ago at the Massachusetts General Hospital, with the

goal of providing all cancer patients with a genetic fingerprint

to guide therapeutic decisions. Lessons learned will be

outlined, and a roadmap to effectively move testing forward

into the Next Gen sequencing era.

5:00 Breakout Discussions (See Web for Details)

6:00 Close of Day

Tuesday, February 12

8:00 am Morning Coffee

Data Management and Analysis

8:10 Chairperson’s Remarks

8:15 Under the Hood of the 1000 Genomes Project

Mark A. DePristo, Ph.D., Associate Director, Medical

and Population Genetics Analysis, Broad Institute of MIT

and Harvard (on behalf of The 1000 Genomes Project

Consortium)

This presentation discusses the evolution of the nextgeneration

sequencing (NGS) data underlying the public

1000 Genomes Project resource, from some of the earliest

technologies of 2009 to today’s state-of-the-art data. It

will also highlight key NGS analytic advances originating

from the Project.

8:45 Delivering Genomic Medicine: Challenges

and Opportunities

Heidi L. Rehm, Ph.D., FACMG, Assistant Professor,

Pathology, BWH and Harvard Medical School; Director,

Laboratory for Molecular Medicine, Partners Healthcare

Center for Personalized Genetic Medicine

This talk will cover the speaker’s experience in offering clinical

sequencing to patients, from disease-targeted panels to whole

genome analyses as well as supporting the interpretation

and delivery of those results to physicians. It will also cover

approaches to data sharing within the community.

9:15 From Sequence Files to

Sponsored by

Physicians Report and the Tools

Needed to Get There

Martin Seifert, Ph.D., CEO,

Genomatix Software

Providing actionable biology from NGS data in a report useful

to the practicing clinician is difficult. Ensuring the report is

accurate, reproducible, and reflects the biology of the patient

is an even larger task. We will show examples of Genomatix’

approach to these issues and how we successfully ensure a

secure, accurate, and reproducible report, bridging the gap

from sequencer to clinician.

9:30 Rapid Identification of

Sponsored by

Disease Causative Mutations

Ali Torkamani, Ph.D., Co-Founder & CSO,

Cypher Genomics

Recent successes in clinical genome sequencing have

highlighted the potential for sequencing to greatly improve

molecular diagnosis and clinical decision-making. However,

these successes have relied upon large bioinformatics teams

and in-depth literature surveys. We will demonstrate how the

Cypher Genomics software service can quickly return a small

set of well-annotated genetic variants most likely to contribute

to a patient’s disease.

10:00 Coffee Break with Exhibit and

Poster Viewing

Getting Genomic Testing to Clinic

10:30 Sequence Data on Demand: Access,

Visualization and Communication of Genome

Sequence Data between Physicians, Researchers,

and Patients

Sitharthan Kamalakaran, Ph.D., Senior Member, Research

Staff, Philips Research North America

Patients’ genome sequences are informative for clinical care

over the patient’s lifetime and not just for the diagnosis at

hand. We present a web-accessible interface for clinicians to

integrate relevant patient genome data in their routine practice

through clinically-framed queries.

11:00 Targeted Next Generation Sponsored by

Sequencing in FFPE Tumor Samples:

Distilling High Quality Information from Low

Quality Samples

Sachin Sah, Senior Scientist, Diagnostics Research

Development, Asuragen, Inc.

SuraSeq™ PCR-based enrichment procedures enable accurate

and sensitive mutation detection from nanogram inputs of

challenging FFPE tumor DNA. Case studies will be presented

that highlight the use of complementary NGS platforms and

novel bioinformatics for discovery and confirmation studies.

NEW

TriConference.com 6

Recommended Programs:

Main Conference

• Personalized Diagnostics

Short Courses

• NGS Data and the Cloud

• PCR Part I: qPCR in Molecular Diagnostics

• NGS in Molecular Pathology

• PCR Part II: Digital PCR Applications and Advances

11:30 Transitioning New Technologies from the Bench to the Bedside: Direct Fetal Testing Using Circulating

Cell-Free DNA

Allan T. Bombard, M.D., CMO, Sequenom

This presentation will address clinical test implementation of new tests in the US, using circulating cell-free DNA for noninvasive

prenatal testing (NIPT) of fetal aneuploidy from maternal plasma as an example.

12:00 Moving Genomic Screening to the Clinic: Next Steps

Bruce R. Korf, M.D., Ph.D., Wayne H. and Sara Crews Finley Chair in Medical Genetics; Professor and Chair,

Department of Genetics; Director, Heflin Center for Genomic Sciences, University of Alabama at Birmingham

Since the sequencing of the human genome there has been an expectation that a flood of advances would find their

way to the clinic, and, indeed, the pace of translation of genomics to clinical application is accelerating. It is likely that the future of

medical care will evolve by the convergence of two disruptive technologies – that of information science and genomics, which, in a

sense can be viewed as one and the same.

12:30 pm Close of Symposium

7 Genomics in Medicine

Hotel Information

Reserve your hotel and save $100 off

your conference registration*

*You must book your reservation under the Tri-Conference

room block for a minimum of 4 nights at the Marriott or the

Intercontinental Hotel. One discount per hotel room.

Conference Venue:

The Moscone North Convention Center

747 Howard Street

San Francisco, CA 94103

http://www.moscone.com

Please visit TriConference.com to make your

reservations online or call the hotel directly to

reserve your sleeping accommodations.You will

need to identify yourself as a Molecular Med Tri-Con

attendee to receive the discounted room rate with

the host hotel. Reservations made after the cut-off

date or after the group room block has been filled

(whichever comes first) will be accepted on a spaceand

rate-availability basis. Rooms are limited, so

please book early.

Sponsorship &

Exhibit Opportunities

CHI offers comprehensive sponsorship packages which include presentation

opportunities, exhibit space and branding, as well as the use of

the pre and post-show delegate lists. Signing on early will allow you to

maximize exposure to hard-to-reach decision makers.

Breakfast & Luncheon Presentations

Opportunities may include a 15 or 30-minute podium presentation

during the main agenda. Boxed lunches are delivered into the main

session room, which guarantees audience attendance and participation.

Packages include: exhibit space, on-site branding, and more.

Invitation-Only VIP Dinner/Private Receptions

Sponsors will select their top prospects from the conference preregistration

list for an evening of networking at the hotel or at a choice

local venue. CHI will extend invitations and deliver prospects. Evening

will be customized according to sponsor’s objectives.

Exhibit

Exhibitors will enjoy facilitated networking opportunities with 3,000

highly-targeted delegates at the overall event. Speak face-to-face with

prospective clients and showcase your latest product, service, or solution.

Inquire about additional branding

opportunities, including our

Valentine’s Day Soiree sponsorship!

Looking for additional ways to drive leads to

your sales team? CHI can help!

We offer clients numerous options for custom lead generation programs

to address their marketing and sales needs, including:

• Live Webinars

• White Papers

• Market Surveys

• Podcasts and More!

For sponsorship & exhibit information, please

contact:

Companies A-K

Jon Stroup, Manager, Business Development

781-972-5483 • jstroup@healthtech.com

Companies L-Z

Joseph Vacca, Manager, Business Development

781-972-5431 • jvacca@healthtech.com

How to Register: TriConference.com

reg@healthtech.com • P: 781.972.5400 or Toll-free in the U.S. 888.999.6288

Please use

keycode GDX F

when registering!

short Courses (Tuesday, Feb 12)

1 Short Course $695 $395

2 Short Courses $995 $695

Diagnostics Channel

P1 Molecular Diagnostics

P2 Personalized Diagnostics

P3 Cancer Molecular Markers

P4 Circulating Tumor Cells

P5 Digital Pathology– NEW

P6 Companion Diagnostics– NEW

Informatics Channel

P13 Bioinformatics

P14 Integrated R&D

Informatics &

Knowledge Management

Cancer Channel

P3 Cancer Molecular Markers

P4 Circulating Tumor Cells

P15 Predictive Pre-Clinical Models

in Oncology – NEW

P10 Oncology Clinical Trials

P9 Cancer Biologics

Clinical Channel

P10 Oncology Clinical Trials

P11 Clinical and

Translational Science

P12 Clinical Sequencing– NEW

Therapeutics Channel

P7 Mastering Medicinal

Chemistry Summit

P9 Cancer Biologics

P11 Clinical and

Translational Science

S1 Targeting Cancer Stem Cells S2 Genomics in Medicine S3 Point-of-Care Diagnostics S4 Quantitative Real-Time PCR S5 Next Generation Pathology

SC10 PCR Part II: Digital PCR Applications and Advances

SC11 Sample Prep and Biorepositories for Cancer Research

SC12 Next-Generation Sequencing in Molecular Pathology:

Challenges and Applications

SC13 Strategies for Companion Diagnostics Development

SC14 Patient-Derived Cancer Tissue Xenograph Models

SC16 Microfluidics Technology and Market Trends

SC17 Open Cloud & Data Science

Afternoon

SC1 Identification & Characterization of Cancer Stem Cells

SC2 Commercialization Boot Camp: Manual for Success in the Molecular Diagnostics Marketplace

SC3 NGS Data and the Cloud

SC4 Best Practices in Personalized and Translational Medicine

SC5 Latest Advances in Molecular Pathology

SC6 Regulatory Approval of a Therapeutic & Companion Diagnostic: Nuts & Bolts

SC7 PCR Part I: qPCR in Molecular Diagnostics

SC8 Data Visualization

SC9 Methods for Synthesis & Screening of Macrocyclic Compound Libraries

SOURCE:

http://www.triconference.com/uploadedFiles/MMTC/13/MMTC_Symposium_Final_GDX.pdf

Read Full Post »


Genome-Wide Detection of Single-Nucleotide and Copy-Number Variation of a Single Human Cell(1)

Reporter, Writer: Stephen J. Williams, Ph.D.

Genome-Wide Detection of Single-Nucleotide and Copy-Number Variation of a Single Human Cell

Word Cloud by Zach Day

Most tumors exhibit a level of diversity, at the cellular, histologic, and even genetic level (2).  This genetic heterogeneity within a tumor has been a focus of recent research efforts to analyze the characteristics, expression patterns, and genetic differences between individual tumor cells.  This genetic diversity is usually manifested as single nucleotide variations (SNV) and copy number variations (CNV), both of which provide selection pressures in both cancer and evolution.

As cancer research and personalized medicine is focused on analyzing this tumor heterogeneity it has become pertinent view the tumor as a heterogeneous population of cells instead of as a homogenous mass.  In, fact, studies have suggested that cancer cell lines growing on plastic in culture, even though thought of as clonogenic, can actually display a varied degree of expression differences between neighboring cells growing on the same dish.  Indeed, cancer stem cells show an asynchronous cell division, for example a parent CD133-positive cell will divide into a CD133-positive and a CD133-negative cell(3). In addition, the discovery that circulating tumor cells (a rare population of circulating cells in the blood) can be prognostic of outcome in cancer such as inflammatory breast cancer(4), it is ever more important to develop methods to analyze single cell populations.

Harvard University researchers, Dr. Chenghang Zong, Sijia Lu, Alec Chapman and Sunney Xie developed a new amplification method utilizing multiple annealing and looping-based amplification cycles (MALBAC)(1).   A quasilinear preamplification process is used on pictograms of DNA genomic fragments (form 10 to 100 kb) isolated from a single cell.   This is performed to reduce the bias associated with nonlinear DNA amplification.  A series of random primers (which the authors termed MALBAC primers, constructed with a common sequence tags) are annealed at low temperature (0 °C). PCR rounds produce semiamplicons.  Further rounds of amplification, after a step of looping the amplicons, result in full amplicons with complementary ends.  When the two ends hybridize to form the looped DNA, this prevents use of this loop structure as a template, therefore leading to a close-to–linear amplification.    The process allows for a higher fidelity of DNA replication and the ability to amplify a whole genome.  The amplicons are then sequenced either by whole-genome sequencing methods using Sanger-sequencing to verify any single nucleotide polymorphisms.  This procedure of MALBAC-amplification resulted in coverage of 85-93% of the genome of a single cell.

As proof of principle, the authors used MALBAC to amplify the DNA of single SW480 cancer cells (picked from a clonally expanded population of a heterogeneous population (the bulk DNA).  Comparison of the MALBAC method versus the MDA method revealed copy number variations (CNV) between three individual cells, which had been picked from the clonally expanded pool. Their results were in agreement with karyotyping studies on the SW480 cell line.  Meticulous quality controls were performed to limit contamination, high false positive rates of SNV detection due to amplification bias, and false positives due to amplification or sequencing errors.

Interestingly, the authors found 35 unique single nucleotide variations which h had occurred from 20 cell divisions from a single SW480 cancer cell.  This resulted in an estimated 49 mutations which occurred in 20 generations, yielding a mutation rate of 2.5 nucleotides per generation.  In addition, the authors were able to map some of these mutations on various chromosomes and perform next-gen sequencing (deep sequencing) to verify the nucleotide mutations and found an unusually high purine-pyrimidine exchange rate.

In a subsequent paper, investigators from the same group at Harvard used this technology to sequence 99 sperm cells from a single individual to study genetic diversity created during meiotic recombination, a mechanism involved in evolution and development(5).

Reference:

1.            Zong, C., Lu, S., Chapman, A. R., and Xie, X. S. (2012) Science 338, 1622-1626

2.            Cooke, S. L., Temple, J., Macarthur, S., Zahra, M. A., Tan, L. T., Crawford, R. A., Ng, C. K., Jimenez-Linan, M., Sala, E., and Brenton, J. D. (2011) British journal of cancer 104, 361-368

3.            Guo, R., Wu, Q., Liu, F., and Wang, Y. (2011) Oncology reports 25, 141-146

4.            Giuliano, M., Giordano, A., Jackson, S., Hess, K. R., De Giorgi, U., Mego, M., Handy, B. C., Ueno, N. T., Alvarez, R. H., De Laurentiis, M., De Placido, S., Valero, V., Hortobagyi, G. N., Reuben, J. M., and Cristofanilli, M. (2011) Breast cancer research : BCR 13, R67

5.            Lu, S., Zong, C., Fan, W., Yang, M., Li, J., Chapman, A. R., Zhu, P., Hu, X., Xu, L., Yan, L., Bai, F., Qiao, J., Tang, F., Li, R., and Xie, X. S. (2012) Science 338, 1627-1630

Other related posts on this website regarding Cancer and Genomics include:

Cancer Genomics – Leading the Way by Cancer Genomics Program at UC Santa Cruz

Identifying Aggressive Breast Cancers by Interpreting the Mathematical Patterns in the Cancer Genome

Read Full Post »


Reporter: Aviva Lev-Ari, PhD, RN

With IBM Help, Coriell Spins off For-Profit Entity to Store Whole-Genome Sequencing Data

Review of Coriell Institute Profile

Personalized Medicine: An Institute Profile – Coriell Institute for Medical Research: Part 3

https://pharmaceuticalintelligence.com/2013/01/13/personalized-medicine-an-institute-profile-coriell-institute-for-medical-research-part-3/

UPDATED on 5/16/2013

The Bank Where Doctors Can Stash Your Genome

A new company offers a “gene vault” for doctors who want to add genomics to patient care.

Genomic sequencing might be more common in medicine if doctors had a simple way to send for the test and keep track of the data.That’s the hope of Coriell Life Sciences in Camden, New Jersey, a startup that grew out of a partnership between the Coriell Institute for Medical Research and IBM. The company wants to facilitate the process of ordering, storing, and interpreting whole-genome-sequence data for doctors. The company launched in January and is now working with different health-care providers to set up its service. “The intent is that the doctor would order a test like any other diagnostic test they order today,” says Scott Megill, president of Coriell Life Sciences. The company would facilitate sequencing the patient’s DNA (through existing sequencing companies such as Illumina or Ion Torrent), store it in its so-called gene vault, and act as the middleman between doctors and companies that offer interpretation services. Finally, “we will return the genetic result in the human readable form back to the electronic medical record so the doctor can read it and interpret it for the patient,” says Megill.

“You need a robust software infrastructure for storing, analyzing, and presenting information,” says Jon Hirsch, who founded Syapse, a California-based company developing software to analyze biological data sets for diagnosing patients. “Until that gets built, you can generate all the data you want, but it’s not going to have any impact outside the few major centers of genomics medicine,” he says.

The company will use a board of scientific advisors to guide them to the best interpretation programs available. “No one company is in position to interpret the entire genome for its meaning,” says Michael Christman, CEO of the Coriell Institute for Medical Research. “But by having one’s sequence in the gene vault, then the physician will be able to order interpretative engines, analogous to apps for the iPhone,” he says. Doctors could order an app to analyze a patient’s genome for DNA variants linked to poor drug response at one point, and later on, order another for variants linked to heart disease.

The cloud-based workflow could help doctors in different locations take advantage of expert interpretations anywhere, says Christman. “This would allow a doctor who’s at a community clinic in Tulsa, Oklahoma, order an interpretation of breast cancer sequences derived at Sloan Kettering,” he says.

But while the cloud offers many conveniences, it carries some potential risks. “I am a bit concerned if we really start to outsource data to the cloud without any regulation,” says Emiliano De Cristofaro, a cryptography scientist with Xerox’s PARC who is developing a genomic data storage and sharing platform. “We must not forget that the sensitivity of genomic information is quite unprecedented,” he says. “The human genome is not only a unique identifier but also contains things about ethnic heritage, predisposition to certain diseases including mental disorders, and many other traits.” Data leaks happen all the time, says Cristofaro, and while you can change your password after a security break, “there’s no way to revoke your genome.”

Keeping the genomic data secure is a key component and is the reason the group began a relationship with IBM, says Megill. The data would be stored at the company’s headquarters and would be available only to limited users—doctors and companies that offer diagnostic or other medical interpretation of the genome, he says.

If a patient changes her health-care provider, the data will remain available for her next physician. Storing the data will be free, says Christman.

http://www.technologyreview.com/news/510901/the-bank-where-doctors-can-stash-your-genome/

January 30, 2013

Originally published Jan. 29.

MOUNTAIN VIEW, Calif. – The Coriell Institute for Medical Research in partnership with IBM has launched a for-profit company that will store consumers’ whole-genome sequencing data.

The goal of the spinoff company, called Coriell Life Sciences, “is to address how will a doctor actually use whole-genome sequences in a clinical setting,” CIMR CEO Michael Christman said at a personalized medicine meeting here this week. After doctors order a whole-genome sequence, which would be provided by a sequencing service provider, Coriell Life Sciences will harmonize and store that data in a gene vault for the patient. Physicians then will be able to order certain interpretive analyses from third parties on the sequence based on the patient’s medical needs.

After planning for 18 months, Coriell and IBM launched Coriell Life Sciences a few weeks ago. Describing the company as the “expert custodians” of whole-genome data, Christman explained that patients’ information may remain in the gene vault, regardless of whether they change jobs or healthcare providers. The patient will own their data stored in the vault and will have the ability to consent to which third parties gain access to the information and for what purpose.

Coriell Life Sciences will not charge patients for storing their data. Patients can consent to allow their de-identified data to be used for research, at which point Coriell will add their information to an aggregate research database that will be used for discovery work. Alternatively, patients can remove their sequence from the vault if they choose.

Physicians that have ordered certain interpretive analysis on patients’ genome sequences will receive the results through electronic medical records. If the healthcare provider doesn’t have an EMR in place, then they can use a web portal interface through Coriell Life Sciences.

If a physician orders genomic interpretation of a patients’ data related to episodic care, however, the third-party interpretation company will have the right to the genome sequence information for performing that specific analysis. “For most collaborators, their access to patient data will be limited to only the subset of the total sequence required by their specific interpretation,” Scott Megill, CEO of the new firm, told PGx Reporter via email. “If an interpretation company has a legitimate, non-commercial research aim that could benefit from the use of large anonymized data sets, they will have an opportunity to utilize aggregate, well-consented data like any other research organization.”

Likening Coriell Life Sciences to Apple’s App Store, Megill noted that the company’s core GeneExchange product will offer a marketplace in which genome interpretation companies can charge “fair market rates” for their services. In turn for providing the sales channel, marketing, storage, data harmonization, and electronic medical records integration, Coriell Life Sciences will charge a brokerage fee for each transaction, he explained. A spokesperson for the company said that these transaction fees will be “baked into the overall cost to the payor” for each individual test.

“The data is harmonized and brokered such that it can be interpreted by a variety of clinical applications,” Christman said.

“No one company is well positioned to interpret the entire genome,” he added. “In principle what this would do is allow a doctor in Tulsa, Oklahoma, to order the cancer analysis application … that was developed at MD Anderson or Sloan Kettering.”

Coriell Life Sciences is also developing an application that will allow doctors to gauge pharmacogenomic associations in a patient’s sequence. The PGx app will be developed based on data collected by Coriell over the last five years through its Personalized Medicine Collaborative research project.

Launched in December 2007 for the lay public, the Personalized Medicine Collaborative aims to study the impact of genome-informed treatment on medical care by genotyping patients and reporting only clinically actionable genomic information. The study has so far enrolled thousands of participants and has research partnerships with Cooper University Hospital, Virtua Health, Fox Chase Cancer Center, and Helix Health (PGx Reporter 6/17/2009).

Similar to the Personalized Medicine Collaborative, the PGx app will initially enable doctors to gauge whether their patients are at risk for dozens of complex conditions and learn how they metabolize commonly prescribed drugs. “We will be expanding this offering to ultimately include several dozen drug efficacy and dosage recommendations,” Megill said.

The need for securing people’s genome data will become more acute as advanced sequencing technologies become part of mainstream medical care. Coriell Life Sciences was conceived “from a clear market need, identified in our work in the Coriell Personalized Medicine Collaborative research study, to provide the critical missing infrastructure required to enable clinical use of genome-informed medicine,” Megill said. “Doctors today have no easy way to order a genetic test, have the resulting sequence data stored in a trusted place for future use, and receive a ‘human readable’ report that can be used by doctors who haven’t been trained as geneticists.”

Coriell Life Sciences’ business model is based on an assumption that community healthcare providers will likely outsource genome sequencing and the storage of the data. “I don’t think you’re going to see the hospitals buying sequencing machines. It is rocket science and there are rocket scientists who are quite good at it,” Christman said. “So, the doctors will need the ability to collect blood and saliva and the access to FedEx. The sequence then needs to go somewhere.”

Furthermore, Coriell Life Sciences will provide doctors with options on the specific types of available data interpretation services.

“Ultimately, the sequence becomes a commodity supply to the interpretation. Doctors do not need to be educated in the value of an Illumina sequence versus a Complete Genomics sequence to order a specific interpretation,” a company spokesperson said. “Coriell Life Sciences will negotiate the best available supplier for sequence data on their behalf using stringent standards for quality and turnaround time.

“The key principle is making it easy for doctors to order tests and receive results that are ‘human readable’ – without needing to be a geneticist.”

IBM has provided technologies for Coriell Life Sciences and has invested an undisclosed amount in the company. Separate from this effort, Coriell is using IBM’s capabilities and systems to store the 1.5 gigabytes of information per person who has partaken in the Personalized Medicine Collaborative, which aims to genotype 100,000 people.

Megill, in line with other industry observers, believes that doctors are much more likely to use personalized treatment strategies if data from genomic testing were integrated into patients’ electronic medical records. In this regard, the partnership with IBM is critical, since IBM technologies are utilized in 75 percent of the world’s electronic medical record systems, he estimated.

Leveraging IBM’s integration and data interchange technologies, Coriell Life Sciences “will build bi-directional data integrations with healthcare systems so that tests can be ordered, phenotypic data can be utilized, and results can be delivered within the context of the patient record,” Megill said.

Coriell Life Sciences’ model is looking ahead to a time when having a whole genome sequence in medical care will be as commonplace as getting an annual physical exam, except one needs to get his genome sequenced only once. Several speakers at the conference in Mountain View discussed how the advent of whole genome sequencing will change patient care and the diagnostics market.

Describing a model very similar to the one being pursued by Coriell Life Sciences, Cliff Reid, CEO of sequencing firm Complete Genomics, discussed how in the future having whole genome sequence testing performed for a patient and then storing the data for future use will reduce the cost of genetic testing dramatically.

“There will be one cost up front [for whole genome sequencing]… and virtually free thereafter,” Reid said. “By storing it in a secure database, the cost of every genetic test after that is pennies and the time to get it is seconds.

“This is a radically different economic and usage profile than what we’re seeing today in the genetics industry,” he added. “This doesn’t fit very well in the current practice.”

Turna Ray is the editor of GenomeWeb’s Pharmacogenomics Reporter. She covers pharmacogenomics, personalized medicine, and companion diagnostics. E-mail Turna Ray or follow her GenomeWeb Twitter account at @PGxReporter.

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Consumer Market for Personal DNA Sequencing: Part 4

Reporter: Aviva Lev-Ari, PhD RN

FDA Warning for the Leader of Consumer Market for Personal DNA Sequencing Part 4

Word Cloud by Daniel Menzin

This Part 4 of the series on Present and Future Frontier of Research in Genomics has been 

UPDATED on 12/6/2013

23andMe Suspends Health Interpretations

December 06, 2013

Direct-to-consumer genetic testing company 23andMe hasstopped offering its health-related test to new customers, bringing it in line with a request from the US Food and Drug Administration.

In letter sent on Nov. 22, FDA said that 23andMe had not adequately responded to its concerns regarding the validity of their Personal Genome Service. The letter instructed 23andMe to “immediately discontinue marketing” the service until it receives authorization from the agency.

According to a post at the company’s blog from CEO Anne Wojcicki, 23andMe customers who purchased their kits on or after Nov. 22 “will not have access to health-related results.” They will, though, have access to ancestry information and their raw genetic data. Wojcicki notes that the customers may have access to the health interpretations in the future depending on FDA marketing authorization. Those customers are also being offered a refund.

Customers who purchased their kits before Nov. 22 will have access to all reports.

“We remain firmly committed to fulfilling our long-term mission to help people everywhere have access to their own genetic data and have the ability to use that information to improve their lives,” a notice at the 23andMe site says.

In a letter appearing in the Wall Street Journal earlier this week, FDA Commissioner Margaret Hamburg wrote that the agency “supports the development of innovative tests.” As an example, she pointed to its recent clearance of sequencing-based testsfrom Illumina.

She added that the agency also understands that some consumers do want to know more about their genomes and their genetic risk of disease, and that a DTC model would let consumers take an active role in their health.

“The agency’s desire to review these particular tests is solely to ensure that they are safe, do what they claim to do and that the results are communicated in a way that a consumer can understand,” Hamburg said.

In a statement, 23andMe’s Wojcicki says that the company remains committed to its ethos of allowing people access to their genetic information. “Our goal is to work cooperatively with the FDA to provide that opportunity in a way that clearly demonstrates the benefit to people and the validity of the science that underlies the test,” Wojcicki adds.

SOURCE

UPDATED on 11/27/2013

FDA Tells Google-Backed 23andMe to Halt DNA Test Service

VIEW VIDEO

http://www.bloomberg.com/news/2013-11-25/fda-tells-google-backed-23andme-to-halt-dna-test-service.html

FDA Letter to 23andME

Department of Health and Human Services logoDepartment of Health and Human Services

Public Health Service
Food and Drug Administration
10903 New Hampshire Avenue
Silver Spring, MD 20993

Nov 22, 2013

Ann Wojcicki
CEO
23andMe, Inc.
1390 Shoreline Way
Mountain View, CA 94043
Document Number: GEN1300666
Re: Personal Genome Service (PGS)
WARNING LETTER
Dear Ms. Wojcicki,
The Food and Drug Administration (FDA) is sending you this letter because you are marketing the 23andMe Saliva Collection Kit and Personal Genome Service (PGS) without marketing clearance or approval in violation of the Federal Food, Drug and Cosmetic Act (the FD&C Act).
This product is a device within the meaning of section 201(h) of the FD&C Act, 21 U.S.C. 321(h), because it is intended for use in the diagnosis of disease or other conditions or in the cure, mitigation, treatment, or prevention of disease, or is intended to affect the structure or function of the body. For example, your company’s website at http://www.23andme.com/health (most recently viewed on November 6, 2013) markets the PGS for providing “health reports on 254 diseases and conditions,” including categories such as “carrier status,” “health risks,” and “drug response,” and specifically as a “first step in prevention” that enables users to “take steps toward mitigating serious diseases” such as diabetes, coronary heart disease, and breast cancer. Most of the intended uses for PGS listed on your website, a list that has grown over time, are medical device uses under section 201(h) of the FD&C Act. Most of these uses have not been classified and thus require premarket approval or de novo classification, as FDA has explained to you on numerous occasions.
Some of the uses for which PGS is intended are particularly concerning, such as assessments for BRCA-related genetic risk and drug responses (e.g., warfarin sensitivity, clopidogrel response, and 5-fluorouracil toxicity) because of the potential health consequences that could result from false positive or false negative assessments for high-risk indications such as these. For instance, if the BRCA-related risk assessment for breast or ovarian cancer reports a false positive, it could lead a patient to undergo prophylactic surgery, chemoprevention, intensive screening, or other morbidity-inducing actions, while a false negative could result in a failure to recognize an actual risk that may exist. Assessments for drug responses carry the risks that patients relying on such tests may begin to self-manage their treatments through dose changes or even abandon certain therapies depending on the outcome of the assessment. For example, false genotype results for your warfarin drug response test could have significant unreasonable risk of illness, injury, or death to the patient due to thrombosis or bleeding events that occur from treatment with a drug at a dose that does not provide the appropriately calibrated anticoagulant effect. These risks are typically mitigated by International Normalized Ratio (INR) management under a physician’s care. The risk of serious injury or death is known to be high when patients are either non-compliant or not properly dosed; combined with the risk that a direct-to-consumer test result may be used by a patient to self-manage, serious concerns are raised if test results are not adequately understood by patients or if incorrect test results are reported.
Your company submitted 510(k)s for PGS on July 2, 2012 and September 4, 2012, for several of these indications for use. However, to date, your company has failed to address the issues described during previous interactions with the Agency or provide the additional information identified in our September 13, 2012 letter for(b)(4) and in our November 20, 2012 letter for (b)(4), as required under 21 CFR 807.87(1). Consequently, the 510(k)s are considered withdrawn, see 21 C.F.R. 807.87(1), as we explained in our letters to you on March 12, 2013 and May 21, 2013.  To date, 23andMe has failed to provide adequate information to support a determination that the PGS is substantially equivalent to a legally marketed predicate for any of the uses for which you are marketing it; no other submission for the PGS device that you are marketing has been provided under section 510(k) of the Act, 21 U.S.C. § 360(k).
The Office of In Vitro Diagnostics and Radiological Health (OIR) has a long history of working with companies to help them come into compliance with the FD&C Act. Since July of 2009, we have been diligently working to help you comply with regulatory requirements regarding safety and effectiveness and obtain marketing authorization for your PGS device. FDA has spent significant time evaluating the intended uses of the PGS to determine whether certain uses might be appropriately classified into class II, thus requiring only 510(k) clearance or de novo classification and not PMA approval, and we have proposed modifications to the device’s labeling that could mitigate risks and render certain intended uses appropriate for de novo classification. Further, we provided ample detailed feedback to 23andMe regarding the types of data it needs to submit for the intended uses of the PGS.  As part of our interactions with you, including more than 14 face-to-face and teleconference meetings, hundreds of email exchanges, and dozens of written communications, we provided you with specific feedback on study protocols and clinical and analytical validation requirements, discussed potential classifications and regulatory pathways (including reasonable submission timelines), provided statistical advice, and discussed potential risk mitigation strategies. As discussed above, FDA is concerned about the public health consequences of inaccurate results from the PGS device; the main purpose of compliance with FDA’s regulatory requirements is to ensure that the tests work.
However, even after these many interactions with 23andMe, we still do not have any assurance that the firm has analytically or clinically validated the PGS for its intended uses, which have expanded from the uses that the firm identified in its submissions. In your letter dated January 9, 2013, you stated that the firm is “completing the additional analytical and clinical validations for the tests that have been submitted” and is “planning extensive labeling studies that will take several months to complete.” Thus, months after you submitted your 510(k)s and more than 5 years after you began marketing, you still had not completed some of the studies and had not even started other studies necessary to support a marketing submission for the PGS. It is now eleven months later, and you have yet to provide FDA with any new information about these tests.  You have not worked with us toward de novo classification, did not provide the additional information we requested necessary to complete review of your 510(k)s, and FDA has not received any communication from 23andMe since May. Instead, we have become aware that you have initiated new marketing campaigns, including television commercials that, together with an increasing list of indications, show that you plan to expand the PGS’s uses and consumer base without obtaining marketing authorization from FDA.
Therefore, 23andMe must immediately discontinue marketing the PGS until such time as it receives FDA marketing authorization for the device. The PGS is in class III under section 513(f) of the FD&C Act, 21 U.S.C. 360c(f). Because there is no approved application for premarket approval in effect pursuant to section 515(a) of the FD&C Act, 21 U.S.C. 360e(a), or an approved application for an investigational device exemption (IDE) under section 520(g) of the FD&C Act, 21 U.S.C. 360j(g), the PGS is adulterated under section 501(f)(1)(B) of the FD&C Act, 21 U.S.C. 351(f)(1)(B).  Additionally, the PGS is misbranded under section 502(o) of the Act, 21 U.S.C. § 352(o), because notice or other information respecting the device was not provided to FDA as required by section 510(k) of the Act, 21 U.S.C. § 360(k).
Please notify this office in writing within fifteen (15) working days from the date you receive this letter of the specific actions you have taken to address all issues noted above. Include documentation of the corrective actions you have taken. If your actions will occur over time, please include a timetable for implementation of those actions. If corrective actions cannot be completed within 15 working days, state the reason for the delay and the time within which the actions will be completed. Failure to take adequate corrective action may result in regulatory action being initiated by the Food and Drug Administration without further notice. These actions include, but are not limited to, seizure, injunction, and civil money penalties.
We have assigned a unique document number that is cited above. The requested information should reference this document number and should be submitted to:
James L. Woods, WO66-5688
Deputy Director
Patient Safety and Product Quality
Office of In vitro Diagnostics and Radiological Health
10903 New Hampshire Avenue
Silver Spring, MD 20993
If you have questions relating to this matter, please feel free to call Courtney Lias, Ph.D. at 301-796-5458, or log onto our web site at www.fda.gov for general information relating to FDA device requirements.
Sincerely yours,
/S/
Alberto Gutierrez
Director
Office of In vitro Diagnostics
and Radiological Health
 Center for Devices and Radiological Health

SOURCE

http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2013/ucm376296.htm

Cancer Diagnostics by Genomic Sequencing: ‘No’ to Sequencing Patient’s DNA, ‘No’ to Sequencing Patient’s Tumor, ‘Yes’ to focus on Gene Mutation Aberration & Analysis of Gene Abnormalities

Symposia

http://aaas.confex.com/aaas/2013/webprogram/start.html

Personal Genetics: An Intersection Between Science, Society, and Policy

Saturday, February 16, 2013: 8:30 AM-11:30 AM

Room 203 (Hynes Convention Center)

On 26 June 2000, scientists announced the completion of a rough draft of the human genome, the result of the $3 billion publicly funded Human Genome Project. In the decade since, the cost of genome sequencing has plummeted, coinciding with the development of deep sequencing technologies and allowing, for the first time, personalized genetic medicine. The advent of personal genetics has profound implications for society that are only beginning to be discussed, even as the technologies are rapidly maturing and entering the market. This symposium will focus on how the genomic revolution may affect our society in coming years and how best to reach out to the general public on these important issues. How has the promise of genomics, as stated early in the last decade, matched the reality we observe today? What are the new promises — and pitfalls — of genomics and personal genetics as of 2013? What are the ethical implications of easy and inexpensive human genome sequencing, particularly with regard to ownership and control of genomic datasets, and what stakeholder interests must be addressed? How can the scientific community engage with the public at large to improve understanding of the science behind these powerful new technologies? The symposium will comprise three 15-minute talks from representatives of relevant sectors (academia/education, journalism, and industry), followed by a 45-minute panel discussion with the speakers.

Organizer:

Peter Yang, Harvard University

Co-organizers:

Brenna Krieger, Harvard University

and Kevin Bonham, Harvard University

Discussant:

James Thornton, Harvard University

Speakers:

 

Ting Wu, Harvard University

Personal Genetics and Education

Mary Carmichael, Boston Globe

The Media and the Personal Genetics Revolution

Brian Naughton, 23andMe Inc.

Commercialization of Personal Genomics: Promise and Potential Pitfalls

Mira Irons, Children’s Hospital Boston

Personal Genomic Medicine: How Physicians Can Adapt to a Genomic World

Sheila Jasanoff, Harvard University

Citizenship and the Personal Genomics

Jonathan Gitlin, National Human Genome Research Institute

Personal Genomics and Science Policy

THIS IS A SERIES OF FOUR POINTS OF VIEW IN SUPPORT OF the Paradigm Shift in Human Genomics

How to Tailor Cancer Therapy to the particular Genetics of a patient’s Cancer

‘No’ to Sequencing Patient’s DNA, ‘No’ to Sequencing Patient’s Tumor, ‘Yes’ to focus on Gene Mutation Aberration & Analysis of Gene Abnormalities PRESENTED in the following FOUR PARTS. Recommended to be read in its entirety for completeness and arrival to the End Point of Present and Future Frontier of Research in Genomics

Part 1:

Research Paradigm Shift in Human Genomics – Predictive Biomarkers and Personalized Medicine

https://pharmaceuticalintelligence.com/2013/01/13/paradigm-shift-in-human-genomics-predictive-biomarkers-and-personalized-medicine-part-1/

Part 2:

LEADERS in the Competitive Space of Genome Sequencing of Genetic Mutations for Therapeutic Drug Selection in Cancer Personalized Treatment

https://pharmaceuticalintelligence.com/2013/01/13/leaders-in-genome-sequencing-of-genetic-mutations-for-therapeutic-drug-selection-in-cancer-personalized-treatment-part-2/

Part 3:

Personalized Medicine: An Institute Profile – Coriell Institute for Medical Research

https://pharmaceuticalintelligence.com/2013/01/13/personalized-medicine-an-institute-profile-coriell-institute-for-medical-research-part-3/

Part 4:

The Consumer Market for Personal DNA Sequencing

 

Part 4:

The Consumer Market for Personal DNA Sequencing

How does 23andMe genotype my DNA?

Technology and Standards

23andMe is a DNA analysis service providing information and tools for individuals to learn about and explore their DNA. We use the Illumina OmniExpress Plus Genotyping BeadChip (shown here). In addition to the variants already included on the chip by Illumina, we’ve included our own, customized set of variants relating to conditions and traits that are interesting. Technical information on the performance of the chip can be found on Illumina’s website.

All of the laboratory testing for 23andMe is done in a CLIA-certified laboratory.

Once our lab receives your sample, DNA is extracted from cheek cells preserved in your saliva. The lab then copies the DNA many times — a process called “amplification” — growing the tiny amount extracted from your saliva until there is enough to be genotyped.

In order to be genotyped, the amplified DNA is “cut” into smaller pieces, which are then applied to our DNA chip, a small glass slide with millions of microscopic “beads” on its surface (read more about this technology). Each bead is attached to a “probe”, a bit of DNA that matches one of the approximately one million genetic variants that we test. The cut pieces of your DNA stick to the matching DNA probes. A fluorescent signal on each probe provides information that can tell us which version of that genetic variant your DNA corresponds to.

Although the human genome is estimated to contain about 10-30 million genetic variants, many of them are correlated due to their proximity to each other. Thus, one genetic variant is often representative of many nearby variants, and the approximately one million variants on our genotyping chip provide very good coverage of common variation across the entire genome.

Our research team has also hand-picked tens of thousands of additional genetic variants linked to various conditions and traits in the scientific literature to analyze on our genotyping chip. As a result we can provide you with personal genetic information available only through 23andMe.

Genetics service 23andMe announced some new cash in the bank today with a $50 million raise from Yuri Milner, 23andMe CEO Anne Wojcicki, Google’s Sergey Brin (who also happens to be Wojcicki’s husband), New Enterprise Associates, MPM Capital, and Google Ventures.

With today’s new funding also comes the reduction of the price of its genome analysis service to $99. This isn’t special holiday pricing (as 23andMe has run repeatedly in the past) the company tells me, but rather what its normal pricing will be from now on.

This move is overdue, at least as far as 23andMe’s business model is concerned. Just yesterday TechCrunch Conference Chair Susan Hobbs told me she was waiting for another $99 pricing deal to buy the Personal Genome Analysis product. Sure 23andMe has experimented with various pricing models, including subscription, since its founding in 2007, but had been at an official and prohibitive $299 price point until today. It’s also apparently been rigorously beta-testing various price points in the past couple of weeks, at some point experimenting with some lower than $99.

For comparison, the company’s original pricing began at $999 and offered subscribers just 14 health and trait reports versus today’s 244 reports, as well as genetic ancestry information. Natera, Counsyl and Pathway Genomics are also in the genomics space, but they work by offering their services through doctors rather than direct to consumer.

Since the company’s launch five years ago, it’s had 180K civilians profile their DNA, and representative Catherine Afarian tells us that, post-price drop and funding, its goal is to reach a million customers in 2013. This is a supremely ambitious goal considering it wants to turn an average user acquisition rate of 36K per year into one of 820K in one year alone.

But Afarian isn’t fazed and brings up how the company once sold out 20k in $99 account inventory on something called “DNA Day.” “Once we can offer the service at $99 it means the average American will buy in,” she said.

That $299 was too pricey, according to Hobbs, but $99 might be just right. She said the $99 price point, which yes, is less than an iPhone, was the main factor in her decision to buy in. “23andMe is more ‘nice-to-know’ information rather than ‘need-to-know’ information. It’s nice to know your ancestry. It’s more of a need to know that you are predisposed genetically for a type of cancer, so that you may take precautionary measures,” she said, implying that the data given by 23andMe isn’t necessarily vital medical information, or actionable when it is. While 23andMe can give you indicators about certain disease risks, it doesn’t close the loop, as in tell you what to do to prevent these diseases.

“Its [utility] depends on your genetic data,” said Afarian when I asked her about the usefulness of the product. “If you’ve got a Factor 5 that puts you at risk for clotting, you might want to invest in anti-clotting socks. [And] there’s always something about themselves that people didn’t know.”

Hobbs said eventually that she wouldn’t buy it, but only because she was looking into more exact lineage information for her little girl, and you need a Y chromosome in all DNA tests to show paternal lineage. Afarian also countered this hesitation, saying that what makes 23andMe unique is that it’s not only looking at just your Y or your mitochondrial DNA, but also your autosomal DNA, which does show some patrilineal information for females who lack that precious Y.

While still sort of a novelty, the potential for 23andMe goes beyond lineage and hopefully that extra $50 million will go further than keeping the price low and into research. The company hopes that a million users will result in a giant database of 23andWe genetic info that can be used to spot trends, like which genes mean a higher risk of diabetes/cancer, etc. Which is great if it happens but for now remains a pipe dream for 23andMe/We.

http://techcrunch.com/2012/12/11/23andnotme/

12/13/2012 @ 5:23PM |6,471 views

What Is 23andMe Really Selling: The Moral Quandary At The Center Of The Personalized Genomics Revolution

This week, 23andme, the personalized genomics company founded by Anne Wojcicki, wife of Google co-founder Sergey Brin, got an influx of investment cash ($50 million). According to their press release, they are using the money to bring the cost of their genetic test down to $99 (it was previously $299) which, they hope, will inspire the masses to get tested.

So should the masses indulge?

I prefer a quantified self approach to this question. At the heart of the quantified self-movement lies a very simple idea: metrics make us better. For devotees, this means “self-tracking,” using everything from the Nike fuel band to the Narcissism Personality Index to gather large quantities of personal data and—the bigger idea—use that data to improve performance.

If you consider that performance suffers when health suffers then a genetic test can been seen as a kind of metric used to improve performance. This strikes me as the best way to evaluate this idea and leads us to ask the same question about personalized genomics that the quantified self movement asks about every other metric: will it improve performance.

Arguments rage all over the place on this one, but the short answer is that SNP tests—which is the kind of DNA scan 23andme relies upon— don’t tell us all that much (yet).  They analyze a million genes out of three billion total and the impact those million play in long term-health outcomes is still in dispute. For example, the nature/nurture split is normally viewed at 30/70—meaning environmental factors play a far more significant role in long-term health outcomes than genetics.

Moreover, all of the performance metrics used by the quantified self movement are used to for behavior modification—to drive self-improvement. Personalized genomics isn’t there yet. As Stanford University’s Nobel Prize-winning RNA researcher Andy Fire once told me, “if someone off the street is looking for pointers on how to live a healthier life, there’s nothing these tests will tell you besides basic physician advice like ‘eat right, don’t smoke and get plenty of exercise.’”

And even with more well-regarded SNP tests, like the ones that examine the BRCA 1 and 2 markers for breast cancer—which  . NYU Langone Medical Center bioethicist Arthur Caplan explains it like this, “Say you test positive for a breast cancer disposition—then what are you going to do? The only preventative step you can take is to chop off your breasts.”

So if prevention is not available the only thing left is fear and anxiety. Unfortunately, in the past few decades, there have been hundreds of studies linking stress to everything from immunological disorders to heart disease to periodonitic troubles. So while finding out you may be at risk for Parkinson’s may make you feel informed, that knowledge isn’t going to stop you from developing the disease—but the resulting stress may contribute to a host of other complications.

This brings up a different question: if personalized genomics can’t yet help us much and could possibly hurt us—where’s the upside?

Turns out there’s a big upside: Citizen science. SNP tests are not yet viable because we need more info. 23andme talks about the “power of one million people,” meaning, if one million take these tests then the resulting genetic database could lead to big research breakthroughs and these could lead to all sorts of health/performance improvements.

This is what 23andme is really selling for $99 bucks a pop—a crowdsourced shot at unraveling a few more DNA mysteries.

And this also means that the question at the heart of the personalized genomics industry is not about metrics at all—it’s about morals: Should I risk my health for the greater good?

http://www.forbes.com/sites/stevenkotler/2012/12/13/what-is-23andme-really-selling-the-moral-quandary-at-the-center-of-the-personalized-genomics-revolution/

You can browse your data for all of the variants we test using the Browse Raw Data feature, or download your data here.

before you buy (59) »

What unexpected things might I learn?

How does 23andMe genotype my DNA?

Can I use the saliva collection kit for infants and toddlers?

getting started (20) »

When and how do I get my data?

How do I collect saliva samples?

How long will it take for my sample to reach the lab?

account/profile settings (20) »

Which Ancestry setting in My Profile should I choose?

How do I use Browse Raw Data?

What do the options under the “Account” link in the upper right-hand corner control?

product features (145) »

I know that a particular person is my relative. What’s the probability that we share a sufficient amount of DNA to be detected by Relative Finder?

What is the average percent DNA shared for different types of cousins?

How does Relative Finder estimate the Predicted Relationship?

research initiatives (8) »

What do I get in return for taking surveys?

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REFERENCES

http://www.foundationmedicine.com/diagnostics-publications.php

http://www.coriell.org/media-center/publications

Http://www.coriell.org/assets/pdfs/gronowski_etal_coriellinstitute_clinicalchemistry2011_humantissuesinresearch.pdf

http://scholar.google.com/scholar?start=10&q=Gene+Mutation+Aberration+%26+Analysis+of+Gene+Abnormalities&hl=en&as_sdt=0,22&as_vis=1

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Curator:  Aviva Lev-Ari, PhD,RN

Cancer Diagnostics by Genomic Sequencing: ‘No’ to Sequencing Patient’s DNA, ‘No’ to Sequencing Patient’s Tumor, ‘Yes’ to focus on Gene Mutation Aberration & Analysis of Gene Abnormalities

How to Tailor Cancer Therapy to the particular Genetics of a patient’s Cancer

THIS IS A SERIES OF FOUR POINTS OF VIEW IN SUPPORT OF the Paradigm Shift in Human Genomics

‘No’ to Sequencing Patient’s DNA, ‘No’ to Sequencing Patient’s Tumor, ‘Yes’ to focus on Gene Mutation Aberration & Analysis of Gene Abnormalities

PRESENTED in the following FOUR PARTS. Recommended to be read in its entirety for completeness and arrival to the End Point of Present and Future Frontier of Research in Genomics

Part 1:

Research Paradigm Shift in Human Genomics – Predictive Biomarkers and Personalized Medicine

https://pharmaceuticalintelligence.com/2013/01/13/paradigm-shift-in-human-genomics-predictive-biomarkers-and-personalized-medicine-part-1/

Part 2:

LEADERS in the Competitive Space of Genome Sequencing of Genetic Mutations for Therapeutic Drug Selection in Cancer Personalized Treatment

https://pharmaceuticalintelligence.com/2013/01/13/leaders-in-genome-sequencing-of-genetic-mutations-for-therapeutic-drug-selection-in-cancer-personalized-treatment-part-2/

Part 3:

Personalized Medicine: An Institute Profile – Coriell Institute for Medical Research

https://pharmaceuticalintelligence.com/2013/01/13/personalized-medicine-an-institute-profile-coriell-institute-for-medical-research-part-3/

Part 4:

The Consumer Market for Personal DNA Sequencing

https://pharmaceuticalintelligence.com/2013/01/13/consumer-market-for-personal-dna-sequencing-part-4/

 

Part 2:

LEADERS in the Competitive Space of Genome Sequencing of Genetic Mutations for Therapeutic Drug Selection in Cancer Personalized Treatment

 

  • Foundation Medicine, a Cambridge, Mass.-based company that sells a $5,800 diagnostic test that uses DNA sequencing to help doctors guess which cancer drugs would be helpful in fighting a particular patient’s tumor.

CAMBRIDGE, Mass., January 8, 2013 – Foundation Medicine, Inc. today announced an expansion of its Series B financing, raising an additional $13.5 million and bringing the total raised in the round to $56 million. The new investors include Bill Gates, Evan Jones and Yuri Milner.

“Advances in understanding the human genome are having a dramatic impact on almost every area of medicine,” said Bill Gates. “Foundation Medicine’s approach in harnessing the power of genomic data to improve care for cancer patients could represent an extremely important step forward in improving routine cancer care. I’m happy to be supporting this quite promising approach.”

http://www.foundationmedicine.com/pdf/news-releases/2013_01_08_FMI_Series_B_Ext_FINAL.pdf

Foundation, which previously listed Kleiner Perkins Caulfield & Byers and Google Ventures, raised $13.5 million in the series B round in which Gates participated, bringing its total take to $56 million. The other investors were Facebook billionaire Yuri Milner, who also recently invested in the personal genomics company 23andMe, and Evan Jones, the diagnostics industry legend who founded DiGene, which was sold to Qiagen for $1.6 billion in 2007. Jones will also join Foundation’s board.

http://www.forbes.com/sites/matthewherper/2013/01/08/bill-gates-invests-in-cancer-dna-sequencing-firm/

It now costs as little as $1,000 to get a fairly accurate readout of the 6 billion letters of DNA code for any single person.

In cancer, the approach right now is usually not to sequence all a patient’s DNA or that of his tumor, but instead to focus on particular genetic mutations in the tumor that might provide clues as to what medicines to try. Major cancer centers are using this approach with patients for whom it’s not obvious which medicine represents the best bet. Foundation’s approach has been to provide that kind of testing to a larger audience. To do so, it uses the DNA sequencing machines made by Illumina and other companies.

“What we want to do is take this testing to the community practices to treat patients where they live,” Michael Pellini, Foundation’s chief executive, 2011.

There is some evidence backing up that test. In a study conducted with the Dana-Farber Cancer Institute and published in Nature Medicine, found that more than half of patients with lung and colon cancer might benefit from the test.  from high-speed tests that detect DNA flaws doctors can target with existing medicines, a study found.

Researchers used a gene test made by closely held Foundation Medicine Inc. to sequence 145 cancer-associated genes in 40 colon tumor samples and 24 lung tumors.

They found that

53 percent of colon tumors and

71 percent of lung tumors

had mutations that may be attacked with cancer medicines on the market or in human trials, according to the study published in Nature Medicine. In some cases, the results revealed what drugs wouldn’t work against the tumors.

The study from researchers at Foundation Medicine and the Dana-Farber Cancer Institute in Boston, shows the value of using DNA sequencing machines to optimize treatment by matching drugs against specific gene abnormalities inside a patient’s tumor, said Pasi Janne, a study co-author.

Finding Gene Abnormalities

Maureen Cronin, a study co-author and molecular pharmacologist at Cambridge, Massachusetts-based Foundation Medicine, said her company was finding new gene abnormalities at a much higher rate than they expected as it performs DNA scans on tumors.

“We expected to find new things, but not at the frequency we are finding them,” she said in a telephone interview. The results “are very surprising.

The study also suggests cancer researchers may need to rethink the way they classify and treat the disease, Cronin said. The particular genetic abnormality inside tumor DNA may matter as much as what organ the tumor came from, she said.

Pfizer is aware of the new lung cancer gene finding and “believes the data are interesting,” said Jenifer Antonacci, a company spokeswoman, in an e-mail.

Laura Woodin, a spokeswoman for London-based AstraZeneca, said the company “is constantly alert to new developments and research in the science of oncology and we review relevant, peer reviewed studies for what they might mean for patients and drug development.”

Foundation Medicine performs a $5,800 test that takes tumor samples and sequences DNA from 200 genes relevant to cancer. It is funded with $33.5 million in venture capital from Third Rock Ventures, Kleiner Perkins Caufield & Byers and Google Ventures, according to its website. $56 Millions on January 8, 2013.

It is difficult to analyze DNA data, Foundation’s test is anything but a full genome, it’s a $6,000 .02% of the genome, showing how much of the problem of using genetic information will need to coming from solving computational and analytical problems — exactly the kind of thing that Bill Gates has always been interested in both at Microsoft and in his work getting lifesaving vaccines to children all around the world.

http://www.bloomberg.com/news/2012-02-12/high-speed-dna-scans-help-most-lung-cancer-patients-study-finds.html

Physicians need to incorporate the latest molecular diagnostic tests to help guide treatment of cancer patients due to the growing number of molecular subtypes that are understood across tumor types.

As more targeted therapies are approved for new molecular subtypes, the number of tests that need to be performed on each patient to determine their subtype increases and very quickly exhausts the very small amount of tumor tissue that is available in routine, clinical samples

Importantly, as patients’ molecular subtypes are more broadly incorporated into physician treatment decisions, we continue to further our understanding of a pathway view of cancer. Patients with different tumor types can have same molecular subtype – often, these therapies are applicable across tumor types since they are targeting the same pathway.

Comprehensive cancer genome analysis to routine cancer care. The company’s initial clinical assay, FoundationOneTM, is a fully informative genomic profile to identify a patient’s individual molecular alterations and match them with relevant targeted therapies and clinical trials.

http://www.foundationmedicine.com/diagnostics.php

The DNA sequencing field has drawn increased interest from pharmaceutical makers focused on developing gene-targeted therapies. Roche Holding AG (ROG), the world’s biggest maker of cancer medicines, last month began a $5.7 billion hostile takeover offer for Illumina Inc., the maker of gene sequencing machines that Foundation Medicine uses in its tests.

  • Pfizer’s Sutent

The researchers also spotted a previously unknown genetic flaw in 2 percent of 561 lung tumors tested. The flaw activates a growth-boosting protein targeted by Pfizer Inc. (PFE)’s kidney- cancer drug Sutent, hinting that the treatment from the New York-based drugmaker may also work in these lung patients, said Janne. He wants to begin a trial of Sutent in lung-cancer patients with the gene change by year end, he said.

Lev-Ari, A. (2012N). Sunitinib (Sutent) brings Adult acute lymphoblastic leukemia (ALL) to Remission – RNA Sequencing – FLT3 Receptor Blockade

https://pharmaceuticalintelligence.com/2012/07/09/sunitinib-brings-adult-all-to-remission-rna-sequencing/

Pfizer’s Kidney Cancer Drug Sutent Effectively caused REMISSION to Adult Acute Lymphoblastic Leukemia (ALL)

https://pharmaceuticalintelligence.com/2012/07/10/pfizers-kidney-cancer-drug-sutent-effectively-caused-remission-to-adult-acute-lymphoblastic-leukemia-all/REMISSION to Adult Acute Lymphoblastic Leukemia (ALL)

REMISSION to Adult Acute Lymphoblastic Leukemia (ALL): Pfizer’s Sutent blocks FLT3 Gene Receptors

https://pharmaceuticalintelligence.com/?s=Pfizer

Researchers in Japan also reported finding the same new genetic change in a fraction of lung tumors, according to two other studies published today in Nature Medicine. Until the three new studies, the genetic change had never been seen in any cancer, said Dr. Pasi Janne.

The change fuses two unrelated genes together to form KIF5B-RET, turning on a growth-driving protein called RET that is usually not active in lung cells.

When Pasi Janne and his collaborators treated cells with the aberrant gene using Pfizer’s Sutent or AstraZeneca Plc (AZN)’s thyroid-cancer drug Caprelsa, the cells died. Both drugs block RET.

http://www.google.com/search?q=pasi+janne+lab&hl=en&tbo=u&tbm=isch&source=univ&sa=X&ei=GzXzUMCyHYSK0QGouoCoAw&ved=0CD8QsAQ&biw=1140&bih=731

Pasi Antero Janne, M.D.,Ph.D.

Harvard Catalyst Profiles

http://connects.catalyst.harvard.edu/profiles/profile/person/711

  1. Yuen HF, Abramczyk O, Montgomery G, Chan KK, Huang YH, Sasazuki T, Shirasawa S, Gopesh S, Chan KW, Fennell D, Janne P, El-Tanani M, Murray JT. Impact of oncogenic driver mutations on feedback between the PI3K and MEK pathways in cancer cells. Biosci Rep. 2012 Aug 1; 32(4):413-22.
    View in: PubMed
  2. Tanizaki J, Okamoto I, Takezawa K, Sakai K, Azuma K, Kuwata K, Yamaguchi H, Hatashita E, Nishio K, Janne PA, Nakagawa K. Combined effect of ALK and MEK inhibitors in EML4-ALK-positive non-small-cell lung cancer cells. Br J Cancer. 2012 Feb 14; 106(4):763-7.
    View in: PubMed
  3. Vogelzang NJ, Benowitz SI, Adams S, Aghajanian C, Chang SM, Dreyer ZE, Janne PA, Ko AH, Masters GA, Odenike O, Patel JD, Roth BJ, Samlowski WE, Seidman AD, Tap WD, Temel JS, Von Roenn JH, Kris MG. Clinical cancer advances 2011: annual report on progress against cancer from the american society of clinical oncology. J Clin Oncol. 2012 Jan 1; 30(1):88-109.
    View in: PubMed
  4. Yuen HF, Chan KK, Grills C, Murray JT, Platt-Higgins A, Eldin OS, O’Byrne K, Janne P, Fennell DA, Johnston PG, Rudland PS, El-Tanani M. Ran Is a Potential Therapeutic Target for Cancer Cells with Molecular Changes Associated with Activation of the PI3K/Akt/mTORC1 and Ras/MEK/ERK Pathways. Clin Cancer Res. 2012 Jan 15; 18(2):380-91.
    View in: PubMed
  5. Hammerman PS, Sos ML, Ramos AH, Xu C, Dutt A, Zhou W, Brace LE, Woods BA, Lin W, Zhang J, Deng X, Lim SM, Heynck S, Peifer M, Simard JR, Lawrence MS, Onofrio RC, Salvesen HB, Seidel D, Zander T, Heuckmann JM, Soltermann A, Moch H, Koker M, Leenders F, Gabler F, Querings S, Ansén S, Brambilla E, Brambilla C, Lorimier P, Brustugun OT, Helland A, Petersen I, Clement JH, Groen H, Timens W, Sietsma H, Stoelben E, Wolf J, Beer DG, Tsao MS, Hanna M, Hatton C, Eck MJ, Janne PA, Johnson BE, Winckler W, Greulich H, Bass AJ, Cho J, Rauh D, Gray NS, Wong KK, Haura EB, Thomas RK, Meyerson M. Mutations in the DDR2 kinase gene identify a novel therapeutic target in squamous cell lung cancer. Cancer Discov. 2011 Jun; 1(1):78-89.
    View in: PubMed
  6. Weisberg E, Choi HG, Ray A, Barrett R, Zhang J, Sim T, Zhou W, Seeliger M, Cameron M, Azam M, Fletcher JA, Debiec-Rychter M, Mayeda M, Moreno D, Kung AL, Janne PA, Khosravi-Far R, Melo JV, Manley PW, Adamia S, Wu C, Gray N, Griffin JD. Discovery of a small-molecule type II inhibitor of wild-type and gatekeeper mutants of BCR-ABL, PDGFRalpha, Kit, and Src kinases: novel type II inhibitor of gatekeeper mutants. Blood. 2010 May 27; 115(21):4206-16.
    View in: PubMed
  7. Beroukhim R, Mermel CH, Porter D, Wei G, Raychaudhuri S, Donovan J, Barretina J, Boehm JS, Dobson J, Urashima M, Mc Henry KT, Pinchback RM, Ligon AH, Cho YJ, Haery L, Greulich H, Reich M, Winckler W, Lawrence MS, Weir BA, Tanaka KE, Chiang DY, Bass AJ, Loo A, Hoffman C, Prensner J, Liefeld T, Gao Q, Yecies D, Signoretti S, Maher E, Kaye FJ, Sasaki H, Tepper JE, Fletcher JA, Tabernero J, Baselga J, Tsao MS, Demichelis F, Rubin MA, Janne PA, Daly MJ, Nucera C, Levine RL, Ebert BL, Gabriel S, Rustgi AK, Antonescu CR, Ladanyi M, Letai A, Garraway LA, Loda M, Beer DG, True LD, Okamoto A, Pomeroy SL, Singer S, Golub TR, Lander ES, Getz G, Sellers WR, Meyerson M. The landscape of somatic copy-number alteration across human cancers. Nature. 2010 Feb 18; 463(7283):899-905.
    View in: PubMed
  8. Qin W, Kozlowski P, Taillon BE, Bouffard P, Holmes AJ, Janne P, Camposano S, Thiele E, Franz D, Kwiatkowski DJ. Ultra deep sequencing detects a low rate of mosaic mutations in tuberous sclerosis complex. Hum Genet. 2010 Mar; 127(5):573-82.
    View in: PubMed
  9. Rodig SJ, Mino-Kenudson M, Dacic S, Yeap BY, Shaw A, Barletta JA, Stubbs H, Law K, Lindeman N, Mark E, Janne PA, Lynch T, Johnson BE, Iafrate AJ, Chirieac LR. Unique clinicopathologic features characterize ALK-rearranged lung adenocarcinoma in the western population. Clin Cancer Res. 2009 Aug 15; 15(16):5216-23.
    View in: PubMed
  10. Lynch TJ, Blumenschein GR, Engelman JA, Espinoza-Delgado I, Govindan R, Hanke J, Hanna NH, Heymach JV, Hirsch FR, Janne PA, Lilenbaum RC, Natale RB, Riely GJ, Sequist LV, Shapiro GI, Shaw A, Shepherd FA, Socinski M, Sorensen AG, Wakelee HA, Weitzman A. Summary statement novel agents in the treatment of lung cancer: Fifth Cambridge Conference assessing opportunities for combination therapy. J Thorac Oncol. 2008 Jun; 3(6 Suppl 2):S107-12.
    View in: PubMed

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