11 February 2007

Exciting Discoveries in Cancer Genetics

Scientists at Cold Spring Harbor Lab have identified a "master control gene" on chromosome 1 whose protein product appears to affect a "tumour suppressor network" with a powerful potential to suppress many types of tumours.
A decades-old cancer mystery has been solved by researchers at Cold Spring Harbor Laboratory (CSHL). "We not only found a critical tumor suppressor gene, but have revealed a master switch for a tumor suppressive network that means more targeted and effective cancer therapy in the future," said CSHL Associate Professor Alea Mills, Ph.D. The study, headed by Mills, was published in the February issue of Cell.

Specifically, Mills' discovery identifies CHD5, a protein that prevents cancer, as a novel tumor suppressor, mapping to a specific portion of chromosome 1 known as 1p36. When CHD5 is not doing its job, the machinery within our cells that normally prevents cancer is switched off. The ability of CHD5 to function as a master switch for a tumor suppressive network suggests that this gene is responsible for a large number of diverse forms of human cancers. "CHD5 functions like a circuit breaker that regulates the tumor-preventing power in our cells—when it blows, cancer occurs," explains Mills. Modulation of CHD5 activity may provide novel strategies for better design of more effective cancer therapies. This gene has remained a mystery until the discovery by Mills' team.
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In addition, a team of researchers at Dana-Farber Cancer Institute and Broad Institute of the Massachusetts Institute of Technology and Harvard University have developed a new rapid screening method for identifying a tumour's genetic profile, in order to target therapies more efficiently.
The findings, published online today on the Nature Genetics Web site, may help relieve a bottleneck between scientists' expanding knowledge of the genetic mutations associated with cancer and the still nascent ability of doctors to use that knowledge to benefit patients. The results constitute an important step toward the era of "personalized medicine," in which cancer therapy will be guided by the particular set of genetic mutations within each patient's tumor, the authors suggest.

....The authors took advantage of a scientific serendipity to devise a simple test to detect important cancer mutations. Mutations in oncogenes (genes linked to cancer) do not occur randomly; rather, they seem to arise most frequently in certain regions of the oncogenes. As a result, researchers didn't necessarily have to scan the entire length of each gene, but could focus instead on the sections most likely to harbor mutations.

They performed these screenings with a technology known as high-throughput genotyping, a fast, relatively inexpensive way of profiling gene mutations within cells. It involves extracting DNA from a tumor sample, copying this material thousands of times, depositing segments of it in tiny "wells" on a small plate, and mixing in reagents that reveal whether each segment carries a specific mutation. Automated equipment then reads the plates to determine which mutations are present in each sample.
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In the future, routine body fluid protein and cellular nucleic acid analysis will identify tumours at a very early stage in their development. Knowing their genetic profile, and understanding how to control the tumour suppressor network, will allow early effective interventions even for what are now the deadliest of cancers.

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