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

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

September 1, 2012 by pkandala

Reporter: Prabodh Kandala, PhD

Word Cloud By Danielle Smolyar

It is now possible to identify aggressive breast cancers by interpreting the mathematical patterns in the cancer genome.

Researchers at the University of Oslo, Norway (UiO) have developed a completely new method for differentiating between breast cancer patients with high and low risks of dying from the illness.

‘Current methods cannot predict who will do well and who will not. We have wanted to identify the very seriously ill patients so that they can receive aggressive treatment’, says Hege Russnes at the Department of Pathology and the Department of Medical Genetics at the Oslo University Hospital and UiO.

To be on the safe side, many breast cancer patients are treated unnecessarily with chemotherapy.

‘Today, many patients receive chemotherapy even though they do not need this treatment. Without the treatment, they would not need to suffer serious side effects. The side effects are sometimes chronic or life-threatening. With our new method, we can distinguish between patients with a good and a poor prognosis. This makes it easier to select the best treatment for the patients’, says oncologist Hans Kristian Vollan in the Department of Oncology and the Department of Medical Genetics at the Oslo University Hospital and UiO.

Finds the changed patterns in the genome

There is much talk about finding the special cancer gene. In reality, it is not that simple. The new method looks at the changes in the genetic material in the cancer cells.

To achieve this, the two medical researchers, along with Head of Research and UiO Professor Anne-Lise Børresen Dale,have begun a close collaboration with Ole Christian Lingjærdein the Department of Informatics at UiO. He is Professor of medical bioinformatics, a new discipline that uses statistics, mathematics and informatics to solve complex problems in cancer biology.

The four researchers have found the statistical connection between changes in cancer genomes and the course of disease for 600 Norwegian breast cancer patients over ten years.

For each patient, they have measured up to 240,000 characteristics of the genome in the cancer cells.

‘We were drowning in information and had to use mathematical and statistical methods to identify the complex changes in the genome. We looked at local areas of the genome where the DNA pieces were shuffled. In some areas, genes are missing. In other areas, there are too many genes. The statistical analyses show that high complexity was clearly associated with increased risk of dying from the disease’, Vollan notes to the research magazine Apollon.

In collaboration with the University of Cambridge, the UiO researchers will now study whether they get the same answers from 2,000 British and Canadian breast cancer samples.

‘If the large study in Cambridge confirms our findings, we and other researchers can pick up the thread and conduct more targeted clinical studies to test whether our method can benefit patients’, says Ole Christian Lingjærde.

This will make it possible to get fast diagnostic answers about the type of breast cancer the patient has.

Today, pathologists use microscopes to diagnose breast cancer and to tell how hard the patient is hit. However, it is impossible to see the complex genome changes in the microscope.

‘Detailed gene analyses and statistical methods will help us move forward. This will be a very important part of the new pathology’, Russness notes.

Gene chaos in cancer cells

The human genome consists of 24 chromosomes. Under normal conditions, each of the 20,000 genes has a fixed place on each of the 24 chromosomes. Each gene consists of a large number of base pairs. A genome has 3.3 billion base pairs.

With the exception of the sex chromosomes, healthy cells always have two copies of the entire gene material. In other words, the number of copies is always the same in two healthy cells.

‘In cancer cells, changes take place in the genome, including changes in the number of copies. The changes can be very local or involve large areas in a chromosome. We have focused on the situation where there are many local changes within a limited area of the genome’, Lingjærde says. His algorithm recognises the area of the genome that has a high number of copies.

Modern treatment

The four Norwegian researchers head the project, together with American, English and Swedish researchers.

They are now further developing the model to identify the exact areas of the genomes and the genes that are most frequently affected by the complex changes in the genome.

The new knowledge can also be important in finding a targeted, molecular treatment for breast cancer.

Ref: http://www.sciencedaily.com/releases/2012/08/120823090952.htm

Posted in Biological Networks, Gene Regulation and Evolution, CANCER BIOLOGY & Innovations in Cancer Therapy | 5 Comments

5 Responses

on September 1, 2012 at 4:16 PM | Reply 2012pharmaceutical

Dr Prabodh,

Very important post. We have several other genome related research categories that this post touches upon. Please, check off what is appropriate

Thank you, please link to Facebook Groups you belong on LinkedIn.

GREAT JOB, all links must be live.

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on September 1, 2012 at 5:29 PM | Reply Identifying Aggressive Breast Cancers by Interpreting the … | Neuro Physiology Blog

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on February 3, 2013 at 1:47 PM | Reply Genome-Wide Detection of Single-Nucleotide and Copy-Number Variation of a Single Human Cell « Pharmaceutical Intelligence

PUT IT IN CONTEXT OF CANCER CELL MOVEMENT

The contraction of skeletal muscle is triggered by nerve impulses, which stimulate the release of Ca2+ from the sarcoplasmic reticuluma specialized network of internal membranes, similar to the endoplasmic reticulum, that stores high concentrations of Ca2+ ions. The release of Ca2+ from the sarcoplasmic reticulum increases the concentration of Ca2+ in the cytosol from approximately 10-7 to 10-5 M. The increased Ca2+ concentration signals muscle contraction via the action of two accessory proteins bound to the actin filaments: tropomyosin and troponin (Figure 11.25). Tropomyosin is a fibrous protein that binds lengthwise along the groove of actin filaments. In striated muscle, each tropomyosin molecule is bound to troponin, which is a complex of three polypeptides: troponin C (Ca2+-binding), troponin I (inhibitory), and troponin T (tropomyosin-binding). When the concentration of Ca2+ is low, the complex of the troponins with tropomyosin blocks the interaction of actin and myosin, so the muscle does not contract. At high concentrations, Ca2+ binding to troponin C shifts the position of the complex, relieving this inhibition and allowing contraction to proceed.

Figure 11.25

Association of tropomyosin and troponins with actin filaments. (A) Tropomyosin binds lengthwise along actin filaments and, in striated muscle, is associated with a complex of three troponins: troponin I (TnI), troponin C (TnC), and troponin T (TnT). In (more) Contractile Assemblies of Actin and Myosin in Nonmuscle Cells

Contractile assemblies of actin and myosin, resembling small-scale versions of muscle fibers, are present also in nonmuscle cells. As in muscle, the actin filaments in these contractile assemblies are interdigitated with bipolar filaments of myosin II, consisting of 15 to 20 myosin II molecules, which produce contraction by sliding the actin filaments relative to one another (Figure 11.26). The actin filaments in contractile bundles in nonmuscle cells are also associated with tropomyosin, which facilitates their interaction with myosin II, probably by competing with filamin for binding sites on actin.

Figure 11.26

Contractile assemblies in nonmuscle cells. Bipolar filaments of myosin II produce contraction by sliding actin filaments in opposite directions. Two examples of contractile assemblies in nonmuscle cells, stress fibers and adhesion belts, were discussed earlier with respect to attachment of the actin cytoskeleton to regions of cell-substrate and cell-cell contacts (see Figures 11.13 and 11.14). The contraction of stress fibers produces tension across the cell, allowing the cell to pull on a substrate (e.g., the extracellular matrix) to which it is anchored. The contraction of adhesion belts alters the shape of epithelial cell sheets: a process that is particularly important during embryonic development, when sheets of epithelial cells fold into structures such as tubes.

The most dramatic example of actin-myosin contraction in nonmuscle cells, however, is provided by cytokinesisthe division of a cell into two following mitosis (Figure 11.27). Toward the end of mitosis in animal cells, a contractile ring consisting of actin filaments and myosin II assembles just underneath the plasma membrane. Its contraction pulls the plasma membrane progressively inward, constricting the center of the cell and pinching it in two. Interestingly, the thickness of the contractile ring remains constant as it contracts, implying that actin filaments disassemble as contraction proceeds. The ring then disperses completely following cell division.

Figure 11.27

Cytokinesis. Following completion of mitosis (nuclear division), a contractile ring consisting of actin filaments and myosin II divides the cell in two.

http://www.ncbi.nlm.nih.gov/books/NBK9961/

This is good. I don’t recall seeing it in the original comment. I am very aware of the actin myosin troponin connection in heart and in skeletal muscle, and I did know about the nonmuscle work. I won’t deal with it now, and I have been working with Aviral now online for 2 hours.

I have had a considerable background from way back in atomic orbital theory, physical chemistry, organic chemistry, and the equilibrium necessary for cations and anions. Despite the calcium role in contraction, I would not discount hypomagnesemia in having a disease role because of the intracellular-extracellular connection. The description you pasted reminds me also of a lecture given a few years ago by the Nobel Laureate that year on the mechanism of cell division.

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on March 2, 2013 at 3:12 PM | Reply recurrence risk for breast cancer | Pharmaceutical Intelligence

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on June 24, 2013 at 7:35 AM | Reply One man’s trash is another man’s treasure, but there is no JUNK after all | Pharmaceutical Intelligence

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