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Clusters of cooperating tumor-suppressor genes are found in large regions deleted in common cancers
Date:5/7/2012

Cold Spring Harbor, NY Scientists at Cold Spring Harbor Laboratory (CSHL) and Memorial Sloan-Kettering Cancer Center have amassed strong experimental evidence implying that commonly occurring large chromosomal deletions that are seen in many cancer types contain areas harboring multiple functionally linked genes whose loss, they posit, confers a survival advantage on growing tumors.

Looking closely at one large deletion -- a so-called copy-number alteration or CNA on 8p, the short arm of chromosome 8 -- in mouse models of human liver cancer, the team validated the presence of a number of genes which normally serve to suppress the formation of tumors, and demonstrated that they act together, and not singly, to suppress tumors. The 8p deletion is commonly seen in human liver cancer and in other epithelial cancers including those of the breast, colon and lung.

The research team, which was co-led by now-adjunct CSHL Professor Scott W. Lowe of Memorial Sloan-Kettering Cancer Center and CSHL Professor Michael Wigler, publishes their results online today in Proceedings of the National Academy of Sciences.

Their hypothesis about the relation between linked tumor suppressor genes in CNAs and tumor survival advantage, if validated in ongoing research, would significantly modify a popular theory of cancer genetics that has stood up since the 1970s. Called the "two-hit" hypothesis, it has helped to explain the behavior of certain cancer genes. All cancers arise from mutations in cancer genes that balance cellular proliferation and suppression of abnormal growth, resulting in out-of-control proliferation, cancer's hallmark.

Some cancers are the result of a single genetic "hit." An example is a single point mutation in the first human oncogene ever discovered, called RAS. It results in the production of an abnormal protein that drives cells to bypass growth checkpoints. The 2-hit hypothesis was proposed to explain aspects
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Contact: Peter Tarr
tarr@cshl.edu
516-367-8455
Cold Spring Harbor Laboratory
Source:Eurekalert

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