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Posts Tagged ‘Dana–Farber Cancer Institute’


Reprogramming Cell in Tissue Repair

Reporter and Curator: Larry H Bernstein, MD, FCAP

This is a novel concept in regenerative medicine that needs attention.

Lin28 enhances tissue repair by reprogramming cellular metabolism

Shyh-Chang N, Zhu H, Yvanka de Soysa T, Shinoda G, Seligson M T, Tsanov K M, Nguyen L, Asara J M, Cantley L C and Daley G Q.

Stem Cell Transplantation Program,Boston Children’s Hospital and Dana Farber Cancer Institute, Boston; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School; Harvard Stem Cell Institute;
Manton Center for Orphan Disease Research; Howard Hughes Medical Institute; Department of Medicine, Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA 02115.

Cell.  7 Nov 2013; 155(4):778-792.    http://dx.doi.org/10.1016/j.cell.2013.09.059.

Lin28 overview

Copyright © 2013 Elsevier Inc.  PMID:     23561442     PMCID:     PMC3652335

Abstract

In recent years, the highly conserved Lin28 RNA-binding proteins have emerged as factors that define stemness in several tissue lineages. Lin28 proteins repress let-7 microRNAs and influence mRNA translation, thereby regulating the self-renewal of mammalian embryonic stem cells. Subsequent discoveries revealed that Lin28a and Lin28b are also important in organismal growth and metabolism, tissue development, somatic reprogramming, and cancer. In this review, we discuss the Lin28 pathway and its regulation, outline its roles in stem cells, tissue development, and pathogenesis, and examine the ramifications for re-engineering mammalian physiology.

Figure 1. Overview of Molecular Mechanisms Underlying Lin28 Function. From: Lin28: Primal Regulator of Growth and Metabolism in Stem Cells.

nihms459462f1  stem cells Lin28

Both Lin28a and Lin28b have been observed to shuttle between the nucleus and cytoplasm, binding both mRNAs and pri-/prelet-7. In the nucleus, Lin28a/b could potentially work in tandem with the heterogeneous nuclear ribonucleoproteins (hnRNPs) to regulate splicing, or with Musashi-1 (Msi1) to block pri-let-7 processing. In the cytoplasm, Lin28a recruits Tut4/7 to oligouridylate pre-let-7, and block Dicer processing to mature let-7 miRNA (right, violet). Lin28a also recruits RNA helicase A (RHA) to regulate mRNA processing in messenger ribonucleoprotein (mRNP) complexes, in tandem with the Igf2bp’s, poly(A)-binding protein (PABP), and the eukaryotic translation initiation factors (eIFs). In response to unknown signals and stimuli, the mRNAs are either shuttled into poly-ribosomes for translation, stress granules for temporary sequestering, or P-bodies for degradation, in part via miRNAs and the Ago2 endonuclease (left, orange).

Figure 2. Signals Upstream and Targets Downstream of Lin28 in the Lin28 Pathway. From: Lin28: Primal Regulator of Growth and Metabolism in Stem Cells.

nihms459462f2  Linm28 stem cell signals

The lin-4 homolog miR-125a/b represses both Lin28a and Lin28b during stem cell differentiation. The core pluripotency transcription factors Oct4, Sox2, Nanog and Tcf3 can activate Lin28a transcription in ESCs and iPSCs, whereas the growth regulator Myc and the inflammation-/stress-responsive NF-κB can transactivate Lin28b. A putative steroid hormone-activated nuclear receptor, conserved from C. elegans daf-12, might also regulate both Lin28a/b and let-7 expression. Downstream of Lin28a/b, the let-7 family represses a network of proto-oncogenes, including the insulin-PI3K-mTOR pathway, Ras, Myc, Hmga2, and the Igf2bp’s. At the same time, Lin28a can also directly bind to and regulate translation of mRNAs, including Igf2bp’s, Igf2, Hmga1, and mRNAs encoding metabolic enzymes, ribosomal peptides, and cell-cycle regulators. Together, this broad network of targets allows Lin28 to program both metabolism and growth to regulate self-renewal.

Figure 3. Potential of Lin28 in Re-Engineering Adult Mammalian Physiology. From: Lin28: Primal Regulator of Growth and Metabolism in Stem Cells.

nihms459462f3  stem cell Lin28

Lin28a, in conjunction with the pluripotency factors Oct4, Sox2 and Nanog, can reprogram somatic cells into iPSCs. Alone, Lin28a/b can reprogram adult HSPCs into a fetal-like state, and enhance insulin sensitivity in the skeletal muscles to improve glucose homeostasis, resist obesity and prevent diabetes. Emergent clues suggest that optimal doses of Lin28a/b might have the potential to re-engineer adult mammalian tissue repair capacities and extend longevity, although Lin28a/b could also cooperate with oncogenes to initiate tumorigenesis. Future work might elucidate these mysteries.

Cell. 2013 Nov 7;155(4):778-92. doi: 10.1016/j.cell.2013.09.059.

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A quartet of Boston-area research centers including Dana-Farber Cancer Institute, Brigham and Women’s Hospital, Boston Children’s Hospital, and the Broad Institute have teamed to create a new Clinical Cancer Genomics Center that will be headquartered at Dana-Farber.

Reporter: Aviva Lev-Ari, PhD, RN

See also

Personalized Cardiovascular Genetic Medicine at Partners HealthCare and Harvard Medical School

November 12, 2013

NEW YORK (GenomeWeb News) – A quartet of Boston-area research centers including Dana-Farber Cancer Institute, Brigham and Women’s Hospital, Boston Children’s Hospital, and the Broad Institute have teamed to create a new clinical cancer genomics center that will be headquartered at Dana-Farber.

Dana-Farber said today that the new Joint Center for Cancer Precision Medicine will harness a wide range of scientific resources and clinical capabilities from the partners to treat cancer patients and feed treatment data into research programs. The multiple capabilities these partners will share and use in the new center include DNA sequencing and other tumor molecular profiling tools, pathology, radiology, surgery, computational interpretation, and tumor modeling systems, they said.

“The center is creating a new capability to use these huge resources in sequencing and pathology and making sure the data gets to caregivers to help customize cancer treatment,” Dana-Farber President Edward Benz said in a statement.

A core part of the center will be a program to obtain and characterize biopsies from patients during treatment by looking at the tumors’ DNA, RNA, and proteins.

The center also will create a computational biology working group that will spread across Dana-Farber, Broad, and Brigham and Women’s Hospital and will include biologists, bioinformaticians, and software designers to develop algorithms aimed at interpreting genome sequencing data.

The partners also plan to support a translational innovation lab that will pursue studies on actionable cancer mutations and drug resistance, as well as preclinical studies of targeted drug combinations. In addition, they will work with members of the Profile cancer genetics research study, a project already launched by Dana-Farber and Brigham and Women’s that is focused on analyzing tumor DNA and creating a database of relevant mutations.

The CanSeq study, a whole-exome sequencing effort involving Dana-Farber, Brigham and Women’s and Broad investigators, will become “an integral part of the new center,” as researchers plan to study the value of whole-exome sequencing in cancer treatment, Dana-Farber said. Currently, the CanSeq partners are sequencing the whole exomes of 50 lung and colon cancer patients as part of a pilot phase.

“This center will allow us to be optimally positioned to answer the big questions in cancer genetics, especially as they affect clinical decision-making,” said Levi Garraway, an associate professor at Dana-Farber and the new center’s director, as well as head of the CanSeq study.

“We seek to understand which genetic and other molecular alterations predict how tumors will respond to targeted drugs, why some patients become resistant to drugs, and what that means about the treatments that should be tried next,” he added.

 

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Rewriting the Mathematics of Tumor Growth[1]; Teams Use Math Models to Sort Drivers from Passengers[2]:  Two JNCI Reviews by Mike Martin Regarding Genomics, Cancer, and Mutation

Curator: Stephen J. Williams, Ph.D.

Recently, there has been extensive interest in the cancer research and oncology community on detecting those mutations responsible for the initiation and propagation of a neoplastic cell (driver mutations) versus those mutations that are randomly (or by selective pressures) acquired due to the genetic instability of the transformed cell.  The impact of either type of mutation has been a topic for debate, with a recent article showing that some passenger mutations may actually be responsible for tumor survival.  In addition many articles, highlighted on this site (and referenced below) in recent years have described the importance of classifying driver and passenger mutations for the purposes of more effective personalized medicine strategies directed against tumors. Two review articles by Mike Martin in the Journal of the National Cancer Institute (JCNI) shed light on the current efforts and successes to discriminate between these passenger and driver mutations and determine impact of each type of mutation to tumor growth.  However, as described in the associated article, the picture is not as clear cut as previously thought and highlights some revolutionary findings. In Rewriting the Mathematics of Tumor Growth, researchers discovered that driver mutations may confer such a small growth advantage that, multiple mutations, including the so called passenger mutations are necessary in order to sustain tumor growth. In fact, much experimental evidence has suggested at least six defined genetic events may be necessary for the in-vitro transformation of human cells.  The following table shows some of the genetic events required for in-vitro transformation in cell culture systems.

Genetic events required for transformation

 Species  Cell type  # of genes required for tumor formation*  Genes used  Reference Events required for priming
Human FibroblastsEmbryonic kidney 3 hTERTH-rasLarge T (a)Hahn(Weinberg) 2LT+hTERT
Mammary epithelialMyoblastsEmbryonic kidney 6 hTERTH-rasP53DDc-myc

cyclin D1CDK4

(b)Kendall(Counter) Hras required for tumorigenesis so probably 5 events needed
Fibroblasts 4 Large TSmall TH-rashTERT (c)Sun(Hornsby) 2Large T + H-ras
Fibroblasts 4 Large TSmall ThTERTRas (d)Rangarajan(Weinberg) 3hTERT, Ras and either small or largeT
Keratinocytes 4 CyclinD1

dnp53

EGFR

c-myc

(e)Goessel(Opitz) 3 for anchorage independence (cyclin D1, dnp53, EGFR),Cyclin D1+dnp53 for immortalization
HOSE 6 CDK4, cyclin D, hTERT plus combination of either P53DD, myrAkt, and H-ras or P53DD, H-ras, c-myc Bcl2 (f)Sasaki(Kiyono) 5
HOSE 3 hTERTSV40 earlyH-ras orK-ras (g)Liu(Bast) 2hTERT+ SV40 early
HOSE 3 Large ThTERTH-ras orc-erB-2 (h)Kusakari(Fujii) 2hTERT+large T
Rat Fibroblasts 2 Large TH-ras (i)Hirakawa Did not analyze
Fibroblasts 2 Large TH-ras (d)Rangarajan(Weinberg) Large T
Mouse MOSEIn p53-/- background 3 c-mycK-rasAkt (j)Orsulic
Pig Fibroblasts 6 p53DDhTERT

CDK4H-ras c-myc

cyclin D1

(k)Adam(Counter) 5 need all butp53DD

Note: priming means events required to immortalize but not fully transform.  * Note that both ability to form colonies in soft agarose and subsequently tested for tumor formation in immunocompromised mice.

a.         Hahn, W. C., Counter, C. M., Lundberg, A. S., Beijersbergen, R. L., Brooks, M. W., and Weinberg, R. A. (1999) Creation of human tumour cells with defined genetic elements, Nature 400, 464-468.

b.         Kendall, S. D., Linardic, C. M., Adam, S. J., and Counter, C. M. (2005) A network of genetic events sufficient to convert normal human cells to a tumorigenic state, Cancer Res 65, 9824-9828.

c.         Sun, B., Chen, M., Hawks, C. L., Pereira-Smith, O. M., and Hornsby, P. J. (2005) The minimal set of genetic alterations required for conversion of primary human fibroblasts to cancer cells in the subrenal capsule assay, Neoplasia 7, 585-593.

d.         Rangarajan, A., Hong, S. J., Gifford, A., and Weinberg, R. A. (2004) Species- and cell type-specific requirements for cellular transformation, Cancer Cell 6, 171-183.

e.         Goessel, G., Quante, M., Hahn, W. C., Harada, H., Heeg, S., Suliman, Y., Doebele, M., von Werder, A., Fulda, C., Nakagawa, H., Rustgi, A. K., Blum, H. E., and Opitz, O. G. (2005) Creating oral squamous cancer cells: a cellular model of oral-esophageal carcinogenesis, Proc Natl Acad Sci U S A 102, 15599-15604.

f.          Sasaki, R., Narisawa-Saito, M., Yugawa, T., Fujita, M., Tashiro, H., Katabuchi, H., and Kiyono, T. (2009) Oncogenic transformation of human ovarian surface epithelial cells with defined cellular oncogenes, Carcinogenesis 30, 423-431.

g.         Liu, J., Yang, G., Thompson-Lanza, J. A., Glassman, A., Hayes, K., Patterson, A., Marquez, R. T., Auersperg, N., Yu, Y., Hahn, W. C., Mills, G. B., and Bast, R. C., Jr. (2004) A genetically defined model for human ovarian cancer, Cancer Res 64, 1655-1663.

h.         Kusakari, T., Kariya, M., Mandai, M., Tsuruta, Y., Hamid, A. A., Fukuhara, K., Nanbu, K., Takakura, K., and Fujii, S. (2003) C-erbB-2 or mutant Ha-ras induced malignant transformation of immortalized human ovarian surface epithelial cells in vitro, Br J Cancer 89, 2293-2298.

i.          Hirakawa, T., and Ruley, H. E. (1988) Rescue of cells from ras oncogene-induced growth arrest by a second, complementing, oncogene, Proc Natl Acad Sci U S A 85, 1519-1523.

j.          Orsulic, S., Li, Y., Soslow, R. A., Vitale-Cross, L. A., Gutkind, J. S., and Varmus, H. E. (2002) Induction of ovarian cancer by defined multiple genetic changes in a mouse model system, Cancer Cell 1, 53-62.

k.         Adam, S. J., Rund, L. A., Kuzmuk, K. N., Zachary, J. F., Schook, L. B., and Counter, C. M. (2007) Genetic induction of tumorigenesis in swine, Oncogene 26, 1038-1045.

However it may be argued that the aforementioned experimental examples were produced in cell lines with a more stable genome than that which is seen in most tumors and had used traditional assays of transformation, such as growth in soft agarose and tumorigenicity in immunocompromised mice, as endpoints of transformation, and not representative of the tumor growth seen in the clinical setting.

Therefore Bert Vogelstein, M.D., along with collaborators around the world developed a model they termed the “sequential driver mutation theory”, in which they describe that driver mutations multiply over time with each mutation “slightly increasing the tumor growth rate through a process that depends on three factors”:

  1. Driver mutation rate
  2. The 0.4% selective growth advantage
  3. Cell division time

This model was based on a combination of experimental data and computer simulations of gliobastoma multiforme and pancreatic adenocarcinoma.  Most tumor models follow a Gompertz kinetics, which show how tumor growth is exponential but eventually levels off over time.

This new theory shows though that a tumor cell with only one driver mutation can only grow so much, until a second driver mutation is required.  Using data for the COSMIC database (Catalog of Somatic Mutations in Cancer) together with analysis software CHASM (Cancer-specific High-throughput Annotation of Somatic Mutations) the researchers analyzed 713 mutations sequenced from 14 glioma patients and 562 mutations in nine pancreatic adenocarcinomas, revealing at least 100 tumor suppressor genes and 100 oncogenes altered.  Therefore, the authors suggested these may be possible driver mutations, or at least mutations required for the sustained growth of these tumors.  Applying this new model to data obtained from Dr. Giardiello’s publication concerning familial adenopolypsis in New England Journal of medicine in 19993 and 2000, the sequential driver mutation model predicted age distribution of FAP patients, number and size of polyps, and polyp growth rate than previous models.  This surprising number of required driver mutations for full transformation was also verified in a study led by University of Texas Southwestern Medical Center biologist Jerry Shay, Ph.D., who noted “this team’s surprise nearly 45% of all colorectal candidate oncogenes (65 mutations) drove malignant proliferation”[3].

However, some investigators do not believe the model is complex enough to account for other factors involved in oncogenesis, such as epigenetic factors like methylation and acetylation.  In addition the review also discusses host and tissue factors which may complicate the models, such as location where a tumor develops.  However, most of the investigators interviewed for this review agreed that focusing on this long-term progression of the disease may give us clues to other potential druggable targets.

Teams Use Math Models to Sort Drivers From Passengers

A related review from Mike Martin in JNCI [2] describes a statistical method, published in 2009 Cancer Informatics[4], which distinguishes chromosomal abnormalities that can drive oncogenesis from passenger abnormalities.  Chromosomal abnormalities, such as deletions, additions, and translocations are common in cancer.  For instance, the well-known Philadelphia chromosome, a translocation between chromosome 9 and 22 which results in the BCR-ABL tyrosine kinase fusion protein is the molecular basis of chronic myelogenous leukemia.

In the report, Eytan Domany, Ph.D., from Weizmann Institute and several colleagues from University of Lausanne, University of Haifa and the Broad Institute were analyzing chromosomal aberrations in a subset of medulloblastoma, which had more gain and losses in chromosomes than had been attributed to the disease.  Using a statistical method they termed a “volumetric sieve”, the investigators were able to identify driver versus passenger aberrations based on three filters:

  • Fraction of patients with the abnormality
  • Length of DNA involved in the aberrant chromosome
  • Abnormality’s copy number

Another method to sort the most “important” chromosomal aberrations from less relevant alterations is termed GISTIC[5], as the website describes is: a tool to identify genes targeted by somatic copy-number alterations (SCNAs) that drive cancer growth (at the Broad Institute website http://www.broadinstitute.org/software/cprg/?q=node/31).  The method allows for comparison across multiple tumors so noise is eliminated and improves consistency of analysis.  This method had been successfully used to determine driver aberrations is mesotheliomas, leukemias, and identify new oncogenes in adenocarcinomas of the lung and squamous cell carcinoma of the esophagus.

Main references for the two Mike Martin articles are as follows:

1.         Martin M: Rewriting the mathematics of tumor growth. Journal of the National Cancer Institute 2011, 103(21):1564-1565.

2.         Martin M: Aberrant chromosomes: teams use math models to sort drivers from passengers. Journal of the National Cancer Institute 2010, 102(6):369-371.

3.         Eskiocak U, Kim SB, Ly P, Roig AI, Biglione S, Komurov K, Cornelius C, Wright WE, White MA, Shay JW: Functional parsing of driver mutations in the colorectal cancer genome reveals numerous suppressors of anchorage-independent growth. Cancer research 2011, 71(13):4359-4365.

4.         Shay T, Lambiv WL, Reiner-Benaim A, Hegi ME, Domany E: Combining chromosomal arm status and significantly aberrant genomic locations reveals new cancer subtypes. Cancer informatics 2009, 7:91-104.

5.         Beroukhim R, Getz G, Nghiemphu L, Barretina J, Hsueh T, Linhart D, Vivanco I, Lee JC, Huang JH, Alexander S et al: Assessing the significance of chromosomal aberrations in cancer: methodology and application to glioma. Proceedings of the National Academy of Sciences of the United States of America 2007, 104(50):20007-20012.

Further posts on CANCER and GENOMICS and Sequencing published on the site include:

The Initiation and Growth of Molecular Biology and Genomics

Inaugural Genomics in Medicine – The Conference Program, 2/11-12/2013, San Francisco, CA

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

Paradigm Shift in Human Genomics – Predictive Biomarkers and Personalized Medicine – Part 1

Breast Cancer: Genomic profiling to predict Survival: Combination of Histopathology and Gene Expression Analysis

Computational Genomics Center: New Unification of Computational Technologies at Stanford

GSK for Personalized Medicine using Cancer Drugs needs Alacris systems biology model to determine the in silico effect of the inhibitor in its “virtual clinical trial”

arrayMap: Genomic Feature Mining of Cancer Entities of Copy Number Abnormalities (CNAs) Data

Comprehensive Genomic Characterization of Squamous Cell Lung Cancers

Mosaicism’ is Associated with Aging and Chronic Diseases like Cancer: detection of genetic mosaicism could be an early marker for detecting cancer.

http://onlinelibrary.wiley.com/doi/10.1111/j.1755-148X.2011.00905.x/full

https://pharmaceuticalintelligence.com/2013/02/05/winning-over-cancer-progression-new-oncology-drugs-to-suppress-driver-mutations-vs-passengers-mutations/

Additional references:

[1] Michor F, Iwasa Y, and Nowak MA (2004) Dynamics of cancer

progression. Nature Reviews Cancer 4, 197-205.

[2] Crespi B and Summers K (2005) Evolutionary biology of cancer.

Trends in Ecology and Evolution 20, 545-552.

[3] Merlo LMF, et al. (2006) Cancer as an evolutionary and ecological

process. Nature Reviews Cancer 6, 924-935.

[4] McFarland C, et al. “Accumulation of deleterious passenger mutations

in cancer,” in preparation.

[5] Birkbak NJ, et al. (2011) Paradoxical relationship between

chromosomal instability and survival outcome in cancer. Cancer

Research 71,3447-3452.

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Reporter: Aviva Lev-Ari, PhD, RN

Aspirin Use, Tumor PIK3CA Mutation, and Colorectal-Cancer Survival

BACKGROUND

Regular use of aspirin after a diagnosis of colon cancer has been associated with a superior clinical outcome. Experimental evidence suggests that inhibition of prostaglandin-endoperoxide synthase 2 (PTGS2) (also known as cyclooxygenase-2) by aspirin down-regulates phosphatidylinositol 3-kinase (PI3K) signaling activity. We hypothesized that the effect of aspirin on survival and prognosis in patients with cancers characterized by mutated PIK3CA (the phosphatidylinositol-4,5-bisphosphonate 3-kinase, catalytic subunit alpha polypeptide gene) might differ from the effect among those with wild-type PIK3CA cancers.

METHODS

We obtained data on 964 patients with rectal or colon cancer from the Nurses’ Health Study and the Health Professionals Follow-up Study, including data on aspirin use after diagnosis and the presence or absence of PIK3CA mutation. We used a Cox proportional-hazards model to compute the multivariate hazard ratio for death. We examined tumor markers, including PTGS2, phosphorylated AKT,KRAS, BRAF, microsatellite instability, CpG island methylator phenotype, and methylation of long interspersed nucleotide element 1.

RESULTS

Among patients with mutated-PIK3CA colorectal cancers, regular use of aspirin after diagnosis was associated with superior colorectal cancer–specific survival (multivariate hazard ratio for cancer-related death, 0.18; 95% confidence interval [CI], 0.06 to 0.61; P<0.001 by the log-rank test) and overall survival (multivariate hazard ratio for death from any cause, 0.54; 95% CI, 0.31 to 0.94; P=0.01 by the log-rank test). In contrast, among patients with wild-type PIK3CA, regular use of aspirin after diagnosis was not associated with colorectal cancer–specific survival (multivariate hazard ratio, 0.96; 95% CI, 0.69 to 1.32; P=0.76 by the log-rank test; P=0.009 for interaction between aspirin and PIK3CA variables) or overall survival (multivariate hazard ratio, 0.94; 95% CI, 0.75 to 1.17; P=0.96 by the log-rank test; P=0.07 for interaction).

CONCLUSIONS

Regular use of aspirin after diagnosis was associated with longer survival among patients with mutated-PIK3CA colorectal cancer, but not among patients with wild-type PIK3CA cancer. The findings from this molecular pathological epidemiology study suggest that thePIK3CA mutation in colorectal cancer may serve as a predictive molecular biomarker for adjuvant aspirin therapy. (Funded by The National Institutes of Health and others.)

SOURCE:

http://www.nejm.org/doi/pdf/10.1056/NEJMoa1207756

Study Shows Aspirin Could Increase Survival in Colorectal Cancer Patients with PIK3CA Mutations

November 28, 2012

By mining epidemiological data from several long-term health studies and combining it with genomic data, a team led by the Dana-Farber Cancer Institute and Harvard Medical School has shown that colorectal cancer patients with PIK3CA mutations may benefit from treatment with aspirin, and that PIK3CA mutation status could serve as biomarker to predict response to aspirin treatment.

The study, published last month in the New England Journal of Medicine, evaluated data from 964 patients with colon or rectal cancer from the Nurses’ Health Study and the Health Professionals Follow-up Study. It found that patients with PIK3CA-mutated cancers who regularly took aspirin after their diagnosis had significantly longer survival, while those with wild-type cancers showed no benefit from aspirin treatment.

According to the researchers, led by Dana Farber’s Shuji Ogino, the results suggest that aspirin might be worth testing as an adjuvant treatment for the approximately 20 percent of colorectal cancer patients with PIK3CA mutations.

“What we conclude is that this PK3CA mutation can be a predictive biomarker and based on molecular testing, doctors could strongly or weakly recommend aspirin,” Ogino told PGx Reporter.

According to the group, numerous observational and other studies have suggested that aspirin might play a protective role in colorectal cancer. Aspirin is currently prescribed to some colorectal cancer patients, Ogino said, but so far there has been no way to predict which patients are likely to actually benefit from it.

Ogino said his team’s previous research found that levels of the enzyme PTGS2 could predict response to aspirin treatment, but the association didn’t reach statistical significance. And because of a lack of good standards for measuring PTGS2 using immunohistochemistry, the group wanted to search for a better, more objective marker.

According to the group, other experiments have suggested that as aspirin inhibits PTGS2 it also down-regulates PI3K signaling, which hinted that PIK3CA mutations could be a potential marker as well.

“Based on previous studies, we hypothesized that PIK3CA mutation may be a good marker for aspirin response,” Ogino said. Testing this hypothesis prospectively, he said, would have taken decades, but by using epidemiological data coupled with molecular data the group was able to find an answer much more quickly.

In the recent NEJM study, Ogino and his colleagues compared the survival of colorectal patients who reported that they regularly used aspirin after their diagnosis with those who didn’t, and further subdivided the group into those with PIK3CA mutations and those without.

The team studied samples from a subset of 964 patients from the two large longitudinal health studies for which the relevant aspirin use data was available, collecting specimens from the registries and using pyrosequencing to establish PIK3CA mutation status for each patient’s tumor. The group also recorded whether samples had BRAF or KRAS mutations.

The researchers found that patients with PIK3CA mutations who reported regular aspirin use had a significantly improved five-year survival rate — 97 percent — over those who didn’t take aspirin — 74 percent.

In contrast, patients without the mutation showed no difference in survival whether they took aspirin regularly or not.

Because the group had previously found that PTGS2 levels were also predictive of response to aspirin use, the researchers evaluated whether a combination of both markers could serve an even greater predictor. According to the study authors, the strongest effect of aspirin use was indeed in patients with both markers, though this finding did not have high statistical significance.

Because the study sampled patients treated before 2006, the group assumed that chemotherapy treatment was similar for the PIK3CA-mutated cases and the wild-type cases. According to the researchers, information on patients’ mutation status was not available to treating physicians at the time of the studies.

The team also distinguished between aspirin use before and after diagnosis, finding that pre-diagnosis use did not seem to influence the relationship between PIK3CA and post-diagnosis aspirin.

Ogino said that the group is pursuing avenues to validate the findings. Unfortunately, relatively few trials of aspirin treatment in colorectal cancer have been conducted.

One option, he said, would be to analyze data from a trial of celecoxib (Pfizer’s Celebrex), a similar drug to aspirin, instead. But it’s not an ideal solution. If the results reflect what the group found in its aspirin study it would shore up the aspirin finding. However, if the results do not match up it would be unclear what that might mean about the group’s original findings.

Potentially, the researchers could also use mouse models or cell lines, but this route has several downsides. Most important, Ogino said, is the fact that aspirin likely affects inflammation more than cancer cells themselves. “Cancer is not just the cancer cell, it’s a much more complicated system so you can’t assess it in the test tube, basically,” he said.

Molika Ashford is a GenomeWeb contributing editor and covers personalized medicine and molecular diagnostics. E-mail her here.

 

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Reporter: Aviva Lev-Ari, PhD, RN

 

ABOUT CGC

The Consumer Genetics Conference covers the key issues facing clinical genetics, personalized medicine, molecular diagnostics, and consumer-targeted DNA applications. It provides a unique outlet where all voices can be heard: pro & con, physician & consumer, research & clinical, academic & corporate, financial & regulatory. CGC is more than just another personalized medicine conference. Since the inaugural meeting in 2009, CGC has been the place where consumer companies learn genomics, and where genomics companies learn how to approach consumers. This year’s event is highlighted by keynote presentations from:

– Kenneth Chahine, Ph.D., J.D., ancestry.com
– Jay Flatley, President and CEO, Illumina
– Lee Silver, Ph.D., Princeton University

Spanning three days, the conference will focus on:
– Day 1: Technology
– Day 2: Business + Translation
– Day 3: Application

And 40+ Cutting-Edge Presentations on:
– Personal Genomics
– Third-Generation Sequencing
– Molecular Diagnostics
– Investment & Funding Opportunities
– Genome Interpretation
– The Future of Personalized Medicine
– Big Data
– Prenatal/Neonatal & Disease Diagnostics
– Empowering Patients
– Nutrition, Food Genetics & Cosmetics

SPEAKERS

Confirmed speakers to date include:

Sandy Aronson, Executive Director of IT, Partners HealthCare Center for Personalized Genetic Medicine (PCPGM)

Arindam Bhattacharjee, Ph.D., CEO and Founder, Parabase Genomics

Diana Bianchi, M.D., Executive Director, Mother Infant Research Institute; Vice Chair for Research, Department of Pediatrics, Floating Hospital for Children, Tufts Medical Center

Cinnamon Bloss, Ph.D., Assistant Professor and Director, Social Sciences and Bioethics, Scripps Translational Science Institute

Alexis Borisy, Partner, Third Rock Ventures

John Boyce, President and CEO, GnuBio

Mike Cariaso, Founder, SNPedia; Author of Promethease

Kenneth Chahine, Ph.D., J.D., Senior Vice President and General Manager, DNA, ancestry.com

Michael Christman, CEO, Coriell Institute for Medical Research

Cindy Crowninshield, RD, LDN, Licensed Registered Dietitian, Body Therapeutics & Sodexo; Founder, Eat2BeWell & Eat4YourGenes; Conference Director, Cambridge Healthtech Institute

Kevin Davies, Ph.D., Editor-in-Chief, Bio-IT World

Chris Dwan, Principal Investigator and Director, Professional Services, BioTeam

Jay Flatley, President & CEO, Illumina

Andrew C. Fish, Executive Director, AdvaMedDx

Dennis Gilbert, Ph.D., Founder, President and CEO, VitaPath Genetics

Rosalynn Gill, Ph.D., Vice President, Clinical Affairs, Boston Heart Diagnostics

Steve Gullans, Managing Director, Excel Venture Management

Don Hardison, President & CEO, Good Start Genetics, Inc.

Richard Kellner, Founder and President, Genome Health Solutions, Inc.

Robert Klein, Ph.D., Chief Business Development Officer, Complete Genomics

Isaac S. Kohane, M.D., Ph.D., Henderson Professor of Health Sciences and Technology, Children’s Hospital and Harvard Medical School; Director, Countway Library of Medicine; Director, i2b2 National Center for Biomedical Computing; Co-Director, HMS Center for Biomedical Informatics

Stan Lapidus, President, CEO and Founder, SynapDx

Gholson Lyon, M.D., Ph.D., Assistant Professor in Human Genetics, Cold Spring Harbor Laboratory; Research Scientist, Utah Foundation for Biomedical Research

Daniel MacArthur, Ph.D., Assistant Professor, Massachusetts General Hospital; Co-founder, Genomes Unzipped

Craig Martin, Chief Executive Officer, Feinstein Kean Healthcare

James McCullough, CEO and Founder, Exosome Diagnostics

Kevin McKernan, CSO, Courtagen Life Sciences

Neil A. Miller, Director of Informatics, Center for Pediatric Genomic Medicine, Children’s Mercy Hospital

Paul Morrison, Ph.D., Laboratory Director, Molecular Biology Core Facilities, Dana-Farber Cancer Institute

Geert-Jan Mulder, M.D., General Partner, Forbion Capital

Steve Murphy, M.D., Managing Partner, Wellspring Total Health

Michael Murray, M.D., Clinical Chief, Genetics Division, Brigham and Women’s Hospital; Instructor, Harvard Medical School, The Harvard Clinical and Translational Science Center

Brian T. Naughton, Ph.D., Founding Scientist, 23andMe

Nathan Pearson, Ph.D., Director of Research, Knome, Inc.

Michael S. Phillips, Ph.D., Canada Research Chair in Translational Pharmacogenomics; Director, Molecular Diagnostic Laboratory, Montreal Heart Institute; Associate Professor, Université de Montréal

John Quackenbush, Ph.D., Professor, Biostatistics and Computational Biology, Cancer Biology Center for Cancer Computational Biology, Dana-Farber Cancer Institute

Martin G. Reese, President and CEO, Omicia

Heidi L. Rehm, Ph.D., FACMG, Chief Laboratory Director, Molecular Medicine, Partners HealthCare Center for Personalized Genetic Medicine (PCPGM); Assistant Professor of Pathology, Harvard Medical School

Oliver Rinner, Ph.D., CEO, BiognoSYS AG

Meredith Salisbury, Senior Consultant, Bioscribe

Marc Salit, Group Leader, Biochemical Science and Multiplexed Biomolecular Science, National Institute of Standards and Technology

Lee Silver, Ph.D., Professor of Molecular Biology and Public Affairs; Faculty Associate, Science, Technology & Environmental Policy Program, Office of Population Research, and the Center for Health and Wellbeing, Woodrow Wilson School, Princeton University

Jamie Streator, Managing Director, Healthcare Investment Banking, Cowen & Company

Joseph V. Thakuria, M.D., MMSc, Attending Physician in Clinical and Biochemical Genetics Medical Genetics, Massachusetts General Hospital; Medical Director, Personal Genome Project; Harvard Catalyst Translational Genetics and Bioinformatics Program, MGH Center for Human Genetics Research

Samuil R. Umansky, M.D., Ph.D., D.Sc., Co-founder, CSO, and President, DiamiR LLC

David A. Weitz, Ph.D., Mallinckrodt Professor of Physics and Applied Physics, Harvard School of Engineering and Applied Sciences

Speaker to be Announced, Barclays

DAY 1: TECHNOLOGY

WEDNESDAY, OCTOBER 3

7:30 am Conference Registration

8:30 Opening Remarks

John Boyce, President and CEO, GnuBIO and Meredith Salisbury, Senior Consultant, Bioscribe

 

OPENING PLENARY SESSION

 

» 8:45 KEYNOTE PRESENTATION

Self-Discovery in the Age of Personal Genomes

Lee Silver, Ph.D., Professor of Molecular Biology and Public Affairs; Faculty Associate, Science, Technology & Environmental Policy Program, Office of Population Research, and the Center for Health and Wellbeing, Woodrow Wilson School, Princeton University

With blinding speed, the biomedical research enterprise is advancing the technology to read personal genomes with greater accuracy, in less time, and at less expense.Meanwhile, consumer genetics has blossomed from infancy to adolescence with an array of innovative consumer-facing products. This unanticipated cottage industry is struggling with growing pains in a mix of conflicted regulators, restless innovators, and demanding consumers. Genetic information, like all information, “wants to be free,” but the commercialization environment is not yet optimized for personal freedom.

 

9:40 The Era of Clinical Sequencing and Personalized Medicine

Michael Christman, CEO, Coriell Institute for Medical Research

Advances in understanding genomic variation and associated clinical phenotypes continue to increase while the cost of full genome sequencing rapidly declines. Having access to your genomic information will become increasingly important as physicians are progressively receptive to incorporating genomics into routine clinical practice. When you need a new prescription, it will be necessary for your physician to quickly and securely access your genetic data to understand drug efficacy prior to dosing. Who will patients and medical professionals trust to store and interpret the data? Coriell is positioned to significantly contribute to the research needed to accelerate the adoption and routine use of genomics in medicine.

 

10:20 FEATURED PRESENTATION

Stan Lapidus, President, CEO and Founder, SynapDx

 

10:50 Coffee Break

 

BIG DATA/ANALYSIS

11:20 IT Infrastructure Required to Manage Patient Genetic Test Results

Sandy Aronson, Executive Director of IT, Partners HealthCare Center for Personalized Genetic Medicine (PCPGM)

There are many challenges associated with getting the maximum value out of a genetic test. This talk will focus on information technology infrastructure that can help.

11:50 Issues in Genomics at Scale

Chris Dwan, Principal Investigator and Director, Professional Services, BioTeam

2012 marks, in many respects, the beginning of the second decade of high-throughput DNA sequencing. Robust, well understood solutions exist for many of the major technical challenges involved in operating a high-throughput genomics facility. Petabyte scale data storage, well suited to research computing in this space, provides a clean example. Certainly it still requires careful planning and thorough engineering to deploy such infrastructure. However, we can now purchase robust systems from multiple vendors rather than having to stitch together solutions in-house. Perhaps more importantly, we can rely on the experience of a community of peers who have been through the exercise before. By contrast, the legal, regulatory, ethical, and privacy concerns in this space have only begun to be explored. As we plan for the coming years, we must certainly plan for technical uncertainty. Technologists find themselves in the role of guessing at the future. As translational medicine, clinical genome sequencing, and other practices become the norm, we must assume extreme and occasionally capricious changes to the social ecosystem. This talk will explore these issues in the context of nearly a decade supporting research computing and genomics for a broad variety of institutions.

12:20 pm Sponsored Presentation (Opportunity Available)

12:50 Luncheon Presentation (Sponsorship Opportunity Available)
or Lunch on Your Own

 

MOLECULAR DIAGNOSTICS

2:05 Panel Discussion
Panelists will first give a brief presentation and then convene for a panel discussion.

Michael S. Phillips, Ph.D., Canada Research Chair in Translational Pharmacogenomics; Director, Molecular Diagnostic Laboratory, Montreal Heart Institute; Associate Professor, Université de Montréal (Moderator)

Molecular Diagnostics and the Patient/Consumer

Andrew C. Fish, Executive Director, AdvaMedDx

This presentation will envision a future in which molecular diagnostics are widely utilized not only for decision making by health professionals, but also for the development and use of a wide range of consumer products that include genetic tests themselves. The speaker will discuss various policy implications of this convergence of patient and consumer interests driven by the expanding availability of molecular diagnostics.

Bridging the Gap between Genetic Risk and Blood Diagnostics by Personalized Health Monitoring

Oliver Rinner, Ph.D., CEO, Biognosys AG

Biognosys has developed a solution to quantify and track protein levels over time from a drop of blood. With a novel mass spectrometric technology, we can record protein signals from 1000s of proteins in a single instrument run and store such digital protein maps in a digital bio-bank that can be screened in silico for known and novel biomarkers. We will provide this technology as personalized health monitoring to patients and consumers that seek actionable information about their state of health.

Measuring Disease Treatment and Progression at the Molecular Level without Biopsy

James McCullough, CEO and Founder, Exosome Diagnostics

Exosome has developed a solution that has the ability to measure, at the molecular level without biopsy, the dynamic nature of both treatment and disease progression. The company has developed a means of isolating exosomes: exosomes are shed into all biofluids, including blood, urine, and CSF, forming a stable source of intact, disease-specific nucleic acids. From these, the company is able to develop predictive gene expression profiles to achieve high sensitivity for rare gene transcripts and the expression of genes responsible for cancers and other diseases. This technology obviates the need for biopsy, and provides a means for detection at a much earlier stage of treatment.

3:20 Refreshment Break

3:50 Sponsored Presentation (Opportunity Available)

 

SEQUENCING

4:20 Panel Discussion

Like a double helix, the future growth of consumer genetics is intimately entwined with technology advances in next-generation sequencing. While the industry excitedly awaits the commercial debut of potentially disruptive nanopore sequencing platforms, existing platforms continue to roll out new enhancements and sequencing strategies that bring us within striking distance of clinical-grade whole genome sequencing. This panel discussion brings together leaders from existing and emerging sequencing providers to present and debate a range of questions including the pros and cons of targeted versus whole-genome sequencing, the emergence of third-generation sequencing platforms, and the challenges of integrating genome sequencing into the clinic.

Paul Morrison, Ph.D., Laboratory Director, Molecular Biology Core Facilities, Dana-Farber Cancer Institute (Moderator)

Panelists:

John Boyce, President and CEO, GnuBIO
Robert Klein, Ph.D., Chief Business Development Officer, Complete Genomics Inc.
Speaker to be Announced, Life Technologies
Speaker to be Announced, Illumina

5:50-6:50 Welcome Reception in the Exhibit Hall with Poster Viewing

 

DAY 2: BUSINESS + TRANSLATION

THURSDAY, OCTOBER 4

7:45 am Morning Coffee

 

TRANSLATIONAL GENOMICS

8:15 Panel Discussion
Panelists will first give a brief presentation and then convene for a panel discussion.

Kevin Davies, Ph.D., Editor-in-Chief, Bio-IT World (Moderator)

All Genomes are Dysfunctional: The Challenges of Interpreting Whole-Genome Data from Healthy Individuals

Daniel MacArthur, Ph.D., Assistant in Genetics, Massachusetts General Hospital; Co-founder, Genomes Unzipped

Recent advances in DNA sequencing technology have made cheap, rapid interrogation of complete genome and exome sequences an almost mundane exercise, and have resulted in significant progress in the discovery of disease-causing sequence changes from the genomes of individuals with rare diseases or cancers. However, such successes do not necessarily translate into an improved ability to use genome-scale data to predict future disease probability for currently healthy individuals. In this presentation I will highlight some of the major technical and analytical challenges associated with developing predictive genomic medicine for the healthy majority.

Consumer Genomics: What do People do with Their Genomes?

Cinnamon Bloss, Ph.D., Assistant Professor and Director, Social Sciences and Bioethics, Scripps Translational Science Institute

Direct-to-consumer personalized genomic testing is controversial, and there are few empirical data to inform the debate regarding use and regulation. The Scripps Genomic Health Initiative is a large longitudinal cohort study of over 2,000 adults who have undergone testing with a commercially available genomic test. Findings from this initiative regarding the psychological, behavioral and clinical impacts of genomic testing on consumers will be presented.

Advances in Noninvasive Prenatal Genetic Testing: Does this Mean “Designer” Babies for All?

Diana Bianchi, M.D., Executive Director, Mother Infant Research Institute; Vice Chair for Research, Department of Pediatrics, Floating Hospital for Children, Tufts Medical Center

Noninvasive prenatal testing for Down syndrome and other chromosome disorders using massively parallel DNA sequencing techniques is now available on a clinical basis in the US. With expected advances in sequencing techniques it will soon be possible to take a blood sample from a pregnant woman and determine if her fetus has a chromosome abnormality or a single gene disorder. How much information do prospective couples want and how do these technical advances affect well-established algorithms for prenatal care?

Translating Genomics into Clinical Care

Heidi L. Rehm, Ph.D., FACMG, Chief Laboratory Director, Molecular Medicine, Partners HealthCare Center for Personalized Genetic Medicine (PCPGM); Assistant Professor of Pathology, Harvard Medical School

This talk will focus on approaches to integrate clinical sequencing into genomic medicine. It will cover next generation sequencing test development from disease panels to whole genomes and the interpretation and reporting of genetic variants identified in patients.

Impact of Genomic Sequencing on Public Health and Preventive Medicine

Joseph V. Thakuria, M.D., MMSc, Attending Physician in Clinical and Biochemical Genetics and Medical Director, Personal Genome Project, Massachusetts General Hospital Center for Human Genetics Research

Early findings in the Personal Genome Project (established by George Church) suggest significant impact for public health and preventive medicine. Solutions to accelerate clinical adoption and address large molecular data challenges will be explored.

9:30 FEATURED PRESENTATION
Genome-in-a-Bottle: Reference Materials and Methods for Confidence in Whole Genome Sequencing

Marc Salit, Group Leader, Biochemical Science and Multiplexed Biomolecular Science, National Institute of Standards and Technology

Genome-in-a-Bottle: Reference Materials and Methods for Confidence in Whole Genome Sequencing Clinical application of ultra high throughput sequencing (UHTS) or “Next Generation Sequencing” for hereditary genetic diseases and oncology is rapidly emerging.  At present, there are no widely accepted genomic standards or quantitative performance metrics for confidence in variant calling. These are needed to achieve the confidence in measurement results expected for sound, reproducible research and regulated applications in the clinic.  NIST has convened the “Genome-in-a-Bottle Consortium” to develop the reference materials, reference methods, and reference data needed to assess confidence in human whole genome variant calls. A principal motivation for this consortium is to develop an infrastructure of widely accepted reference materials and accompanying performance metrics to provide a strong scientific foundation for the development of regulations and professional standards for clinical sequencing.

10:00 Coffee Break in the Exhibit Hall with Poster Viewing

 

VENTURE CAPITAL & INVESTMENT BANKING

10:30 Panel Discussion

This “Funding to IPO Panel” consists of some of the top venture capitalists and investment bankers in therapeutics, diagnostics, and consumer genetics. This series of presentations and follow-on panel, will take attendees through the financial cycle – from funding to IPO, with VC’s and bankers highlighting the corporate criteria most important to them, and the metrics by which they make their decisions.
Panelists:

Geert-Jan Mulder, M.D., General Partner, Forbion Capital

Alexis Borisy, Partner, Third Rock Ventures

Steve Gullans, Managing Director, Excel Venture Management

Jamie Streator, Managing Director, Healthcare Investment Banking, Cowen & Company

Speaker to be Announced, Barclays

12:15 pm Luncheon Presentation (Sponsorship Opportunity Available)
or Lunch on Your Own

 

GENOME DATA: THE PHYSICIAN’S PERSPECTIVE

1:45 Panel Discussion

While making the effort to deploy genomics and sequence data in preventative and clinical care is a noble cause, it is also one that requires pragmatic solutions. This panel discussion will address practical issues related to the day-to-day use of genomic technologies in the clinic — from hospital to private practice to academia.

Steve Murphy, M.D., Managing Partner, Wellspring Total Health (Moderator)
Panelists:

Michael Murray, M.D., Clinical Chief, Genetics Division, Brigham and Women’s Hospital; Instructor, Harvard Medical School, The Harvard Clinical and Translational Science Center

Isaac Samuel Kohane, M.D., Ph.D., Henderson Professor of Health Sciences and Technology, Children’s Hospital and Harvard Medical School; Director, Countway Library of Medicine; Director, i2b2 National Center for Biomedical Computing; Co-Director, HMS Center for Biomedical Informatics

3:00 Refreshment Break in the Exhibit Hall with Poster Viewing

 

GENOME INTERPRETATION

3:30 Omicia: Interpreting Genomes for Clinical Relevance

Martin G. Reese, President and CEO, Omicia

Automatic annotation of variants and integration of disparate data sources is just the first step in the eventual adoption of genomes into clinical practice. The next step is reducing this complexity into the very few, actionable clinically relevant findings. We will show how we integrate such methods within an automated, comprehensive and easy-to-use platform for the interpretation of individual genome data. This system allows for prioritizing variants with respect to its potential clinical impact and is preloaded with clinical gene sets and proprietary annotations to enhance discovery and reporting of personal genes and variants. Furthermore, it is extensible and allows the integration of the user’s proprietary gene and variants sets. We will show several exome and genome analyses.

3:50 Personalized Genomic Interpretation with SNPedia and Promethease

Mike Cariaso, Founder, SNPedia; Author of Promethease

With whole genome prices falling and microarray genotyping accessible to ordinary people over the internet, the challenge is no longer in acquiring the raw data, but in interpreting and using it. In this talk, I will outline a freely available database of literature, organized by the relevant DNA position and phenotypic effects. A complementary analysis program reads raw genomic data and produces a hyperlinked and searchable report of known associations. It can also perform special processing of family trios (child, mother, father), make predictions about offspring, and identify shared ancestry.

4:10 GenoSpace: Creating an Information Ecosystem for 21st Century Genomic Medicine

John Quackenbush, Ph.D., Professor, Biostatistics and Computational Biology, Cancer Biology Center for Cancer Computational Biology, Dana-Farber Cancer Institute

New sequencing technologies are driving the cost of genomic data generation to unprecedented lows, making sequencing available as a potentially valuable clinical and diagnostic tool. The challenge is solving “the last 100 yards” problem–delivering the data to those who need to access it in a manner in which they can use it effectively. GenoSpace has developed technology to connect the diverse consumers and producers of genomic data, creating an ecosystem in which we have the potential to advance genomic medicine.

 

VISIONS FOR PERSONALIZED MEDICINE

 

» 4:30 KEYNOTE PRESENTATION

The Big Picture: Visions for Personalized Medicine

Jay Flatley, President and CEO, Illumina

 

Illumnia logo small5:30 Social Event and Party

 

DAY 3: APPLICATIONS

FRIDAY, OCTOBER 5

8:00 am Morning Coffee

» 8:30 KEYNOTE PRESENTATION 

An Inside Look at How AncestryDNA Uses Population Genetics to Enrich Its Online Family History Experience

Kenneth Chahine, Ph.D., J.D., Senior Vice President & General Manager, DNA, ancestry.com

Ancestry.com is the world’s largest online resource for family history with an extensive collection of over 10 billion historical records that are digitized, indexed and made available online over the past 13 years. In May 2012, AncestryDNA launched a direct-to-consumer genealogical DNA test that delivers two results to customers. The first result predicts identity-by-descent and allows the customer to find genetic relatives within the AncestryDNA customer database. The second determines the customer’s admixture to provide a predicted genetic ethnicity using a state-of-the-art algorithm. The AncestryDNA team leverages pedigrees, documents, geographical information and its extensive biobank of worldwide DNA samples to conduct innovative research in population genetics and translates the complexities of genetic science into a simple, understandable, and meaningful user experience.

 

9:15 Past, Present and Future of Consumer Genetics, a Pioneer’s Perspective

Rosalynn Gill, Ph.D., Vice President, Clinical Affairs, Boston Heart Diagnostics

The first consumer genetics company, Sciona, founded by Rosaylnn Gill, launched its services in April 2001 in the UK in what was either a breakthrough in innovation or an act of incredible naiveté. Twelve years later, many lessons have been learned, but the jury is still out on the appropriate regulatory framework, the necessary industry standards and what constitutes a sustainable business model.

9:45 Sponsored Presentation (Opportunity Available)

10:15 Coffee Break in the Exhibit Hall with Poster Viewing

 

PRENATAL/NEONATAL DIAGNOSTICS 

10:45 Panel Discussion

Panelists will first give a brief presentation and then convene for a panel discussion.

Meredith Salisbury, Senior Consultant, Bioscribe (Moderator)

Neonatal Genomic Medicine

Neil A. Miller, Director of Informatics, Center for Pediatric Genomic Medicine, Children’s Mercy Hospital

The causal gene is known for more than 3,500 monogenic diseases. Many of these can present in the neonatal period, causing up to 30% of neonatal intensive care unit admissions. In the last six months, we have started to offer very rapid diagnostic testing for these diseases at Children’s Mercy Hospital based on genome sequencing. The emerging indications and utility of neonatal genomic medicine will be discussed.

Screening Neonates by Targeted Next-Generation DNA Sequencing

Arindam Bhattacharjee, Ph.D., CEO and Founder, Parabase Genomics

We are developing a neonatal genome sequencing test that will allow screening and diagnosis of primarily newborns and infants affected with a disease or condition allowing prompt treatment. The current approach of DNA based genetic screening for symptomatic and high-risk is not focused around neonates, and so healthcare providers and parents are unable to understand the cause and treatment of the condition in absence of clear symptoms. Our test is unique in that it simultaneously screens and/or diagnoses hundreds of these conditions at once from a single sample, providing more comprehensive information to families and their physicians. It is yet affordable, and provides access to the high-resolution sequence data.

Using NGS Sequencing to Improve the Standard of Care for Routine Genetic Carrier Screening

Don Hardison, President & CEO, Good Start Genetics, Inc.

11:45 Luncheon Presentation (Sponsorship Opportunity Available)
or Lunch on Your Own

 

NUTRITION, FOOD GENETICS & COSMETICS

1:00 The Importance of Genetic Testing-Directed Vitamin Use

Dennis Gilbert, Ph.D., Founder, President and CEO, VitaPath Genetics

VitaPath Genetics, Inc. has developed a platform for genomic-based tests that determine the need for vitamin therapy in medically actionable conditions. Using its platform, VitaPath can develop specific vitamin-remediated risk assays that help manage the use of the $30 billion spent on supplements in the U.S. each year. The first test developed by VitaPath measures genetic risk factors associated with the spina bifida to identify women who would benefit from low-risk, prescription strength folic acid supplementation.

1:20 Using Weight Management Genetic Testing in Nutrition Counseling:
A Dietitian Weighs in on the Matter

Cindy Crowninshield, RD, LDN, Licensed Registered Dietitian, Body Therapeutics & Sodexo; Founder, Eat2BeWell & Eat4YourGenes; Conference Director, Cambridge Healthtech Institute

Between January-July 2012, 15 patients took a weight management genetic test to support their weight loss efforts. An individualized nutrition plan based on their eating and lifestyle habits and test results was created for each person. Data and several case studies will be presented to show how successful these patients were in achieving their weight loss goals. Challenges and opportunities will be discussed. Also presented will be tips and suggestions for genetic testing companies on how they can work best with a private practitioner’s office.

1:40 How Microfluidics is Changing the Landscape of Personalized Cosmetics

David A. Weitz, Ph.D., Mallinckrodt Professor of Physics and Applied Physics, Harvard School of Engineering and Applied Sciences

2:00 Refreshment Break in the Exhibit Hall with Poster Viewing

 

DISEASE DIAGNOSTICS

2:30 Clinical Sequencing and Mitochondrial Disease

Kevin McKernan, CSO, Courtagen Life Sciences

We describe the results from sequencing 64 patients’ Mitochondrial genomes in conjunction with 1,100 nuclear genes. Complementing this data with multiplex ELISA assays to monitor protein levels in the blood can provide additional insight to variants of unknown significance and aid therapeutic decisions.

2:50 A Paradigm Shift: Universal Screening Test

Samuil R. Umansky, M.D., Ph.D., D.Sc., Co-founder, CSO, and President, DiamiR LLC

We will present a fundamentally new approach to the development of a screening test aimed at diseases of various organ systems, organs and tissues. The test is non-invasive and cost efficient. The data we will present demonstrate the potential of our approach for early detection of neurodegenerative diseases, cancer and inflammatory diseases of gastrointestinal and pulmonary systems.

 

THE EMPOWERED PATIENT

3:10 Genomes R Us – How Personalized Medicine is Reshaping the Role of Patients, and Why It Matters

Craig Martin, CEO, Feinstein Kean Healthcare

Much has been said about the advancements in science underlying the genomic revolution. We are beginning now to see the impact at the clinical level, and there’s more to come in the pipeline. But what does this shift in medicine do to change the role of the patient? This presentation provides insights into how best to engage with patient communities to expedite research, commercialization and market impact of innovative technologies, diagnostics and treatments, and to help validate the relative efficacy of such advancements in a value-driven world.

3:40 Consumer Empowerment in Health Care and Personal Genomics: Ethical, Societal and Regulatory Considerations

Gholson Lyon, M.D., Ph.D., Assistant Professor in Human Genetics, Cold Spring Harbor Laboratory; Research Scientist, Utah Foundation for Biomedical Research

The pace of exome and genome sequencing is accelerating with the identification of many new disease-causing mutations in research settings, and it is likely that whole exome or genome sequencing could have a major impact in the clinical arena in the relatively near future. However, the human genomics community is currently facing several challenges, including phenotyping, sample collection, sequencing strategies, bioinformatics analysis, biological validation of variant function, clinical interpretation and validity of variant data, and delivery of genomic information to various constituents. I will review these challenges, with an eye toward consumer genetics.

4:10 It Hurts Less If You Know More: An Empowered Patient’s Diagnostic Odyssey

Richard Kellner, Co-Founder and President, Genome Health Solutions, Inc.

For the early detection, diagnosis and treatment of cancer, there is a wide gap between current “standards of care” and what is possible through the use of advanced genomic technologies. Over the past two years I learned this lesson first hand through personal experiences involving myself, close friends and family members. My story is one of serendipity, frustration and then hope. I learned that, unfortunately, where you live and who you know can greatly influence your quality of care. I also learned that you can overcome these limitations by becoming an “empowered patient” who actively seeks out doctors who are willing to get outside of their comfort zones and practice “participatory medicine,” sometimes at the cutting edge of new precision diagnostics. I will present a new roadmap that both patients and doctors can follow toward a new era of personalized genomic medicine.

 

COMPANIES THAT EMPOWER THE PATIENT

4:40 23andMe’s DTC Exome

Brian T. Naughton, Ph.D., Founding Scientist, 23andMe

In October 2011, 23andMe launched a $999 direct-to-consumer exome product to a limited group of customers.This talk presents findings from this project, including the ubiquitous issue of variants of unknown significance.

5:10 Winding the Asklepian Wand: The Advent of Whole Genomes in Healthcare

Nathan Pearson, Ph.D., Director of Research, Knome, Inc.

With ever cheaper sequencing, richer reference data, and sharper interpretation methods, the clinical use of whole genomes is taking root in pediatrics, oncology, and beyond. Our genomes will ultimately join other cornerstones of clinical care, helping us stay healthier from birth to old age. But that prospect will require fast, robust pipelines that smartly interpret genomes, in the context of good phenotype data, and feed decisive insights back to patients and caregivers. Learn how Knome is making that happen.

5:40 Close of Conference

Source:

http://www.consumergeneticsconference.com/cgc_content.aspx?id=117407&libID=117355

 

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