Early Findings Of Cancer Genome Atlas Map For Glioblastoma To Be Presented At BIO International Convention

Main Category: Cancer / Oncology
Also Included In: Genetics
Article Date: 13 May 2008 - 3:00 PDT

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Cancers will be much more effectively treated when physicians can determine all of the responsible genetic changes in a tumor and how they react and interact in response to specific treatment(s), according to one of the leading scientists who will be speaking at the BIO 2008 International Convention.

On Tuesday, June 17 in a session titled, "Genomics Drives Disruptive Innovations in Biotechnology," Lynda Chin, M.D., physician and scientist at the Dana-Farber Cancer Institute and Harvard Medical School in Boston, will speak about The Cancer Genome Atlas (TCGA) project, a national effort to catalogue all relevant genetic alterations in cancer. Dr. Chin also led the working group on clinical and pathology issues in the planning of the new International Cancer Genome Consortium.

In its pilot phase, TCGA aims to fully characterize all dimensions of the genomes in three cancer types: glioblastoma, ovarian and lung cancers. Dr. Chin, who heads the glioblastoma disease working group in TCGA, will present the atlas' early results on glioblastoma, the most common form of brain cancer in adults and one of the most difficult malignancies to treat effectively.

The other session speakers will be Francis S. Collins, M.D., Ph.D., director of the National Human Genome Research Institute, and Elaine R. Mardis, Ph.D., co-director of the Genome Sequencing Center at Washington University School of Medicine.

The National Institutes of Health-sponsored TCGA is designed to generate the most detailed description yet achieved of the multitude of molecular, or genomic, alterations that characterize cancer. It is the general consensus that only a fraction of the genes causing cancer is known, and even less is understood of their functions. Therefore, the effort of TCGA is much needed as it is the critical first step in the war against cancers.

The genomes of cancer cells typically are altered in the following ways:

- Too few or too many copies of one or more genes.

- Mutations: misspellings in a gene's chemical recipe for a vital protein.

- Structural rearrangements of chromosomal regions that create translocation leading to cancer-causing abnormal gene products (for example, the "Philadelphia chromosome," that triggers chronic myelogenous leukemia).

- Epigenetic silencing or hyper-activation of a cancer gene's expression. A tumor suppressor gene, for example, can be epigenetically silenced in many forms of cancer. As a result, the gene is unable to signal the body to manufacture the tumor suppressor protein that arrests the growth and survival of aspiring cancer cells.

These alterations can affect hundreds to thousands of the protein-coding and non-coding genes and regulatory elements that collectively and cooperatively lead to the development of cancers and influence a cancer's progression, including metastasis, or spread, to other body tissues.

By cataloguing all changes in cancers, TCGA will provide the crucial information about patterns of genomic alterations that will not only lead to identification of therapeutic targets for drug development but also development of molecular biomarkers that can help physicians determine what drug to give for which patients. However, translating genomic discoveries from TCGA into clinical endpoints of therapeutics and diagnostics will not be simple.

First of all, not all changes identified in the cancer genome are equally important or relevant, said Dr. Chin. Many of the changes may simply be the consequences of the inherent instability of cancer genomes - a process that can generate random changes, of which only a minority may be true disease-driving events. Thus, Dr. Chin and her colleagues at TCGA must distinguish the genomic alterations that are the true culprits from those that are just bystanders. "We need to be able to discriminate between alterations that truly are mission-critical to the disease and those that are not," she said.

"We're increasingly coming to appreciate that cancer genes are functionally linked to each other in a cancer-relevant pathway, and that each pathway also has multiple tentacles reaching out to other pathways that together operate cooperatively to endow cancer cells with a range of biological capabilities needed for malignancy," said Dr. Chin. Thus, effective treatment of cancers cannot rely on inhibiting single pathways, but must anticipate how the network would react. Generating a complete atlas of mutational changes is critical to achieve this important goal.

Therefore, Dr. Chin emphasizes that the completion of a map of this cancer network will be only the starting point because elucidation of the biological interaction and relationship between and among these cancer nodes will be necessary to interpret and anticipate the response of this network to various treatments.

In other words, the genetic map of cancer that ultimately emerges from coordinated comprehensive efforts such as TCGA will require downstream disease-based "functionalization," so that viable and rational therapeutic or diagnostic targets for each form of cancer can be identified for biotechnology research and development.

http://www.bio2008.org