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

of a childhood eye cancer called retinoblastoma. Children with the inherited disease developed the disease early --- often in both eyes, whereas children who had the non-inherited, or sporadic form of the disease, developed it later and usually in one eye. It turned out that the inherited disease was caused by a recessive mutation in a single gene called RB1 but that the remaining, normal copy of the gene had to be lost in order for the disease process to begin. (We have two copies of most genes, one inherited from each parent.) The sporadic, non-inherited form of the disease required two hits of the RB1 gene, one of which was loss of a large region containing the gene.

This 2-hit model, which brilliantly explained retinoblastoma and some other cancers, "has also been used to explain what happens when all large chromosomal areas are lost in cancer something that happens quite frequently," notes Associate Professor Scott Powers, a CSHL geneticist and participant in the research published today.

"But the theory can't explain many of these large deletion events, for several reasons," Powers explains. "Most important, the deleted region often does not appear to contain a 'driver' tumor suppressor gene [like RB1] with a point mutation that would constitute the first 'hit.'" Lowe's lab at CSHL used the common 8p deletion to explore in mouse models of liver cancer what might be going on. Specifically, they asked a classic question in cancer: What selective advantage does the 8p deletion provide to the tumor?

In other words, when the 8p deletion occurs, how is a tumor's development aided? What new advantage do the affected cancer cells obtain?

The team found multiple genes within 8p and in adjacent areas of chromosome 8 that function cooperatively to inhibit the formation of tumors. They used RNA interference technology to show that the co-suppression of these linked sets of genes could "synergistically promote tumor growth
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Contact: Peter Tarr
tarr@cshl.edu
516-367-8455
Cold Spring Harbor Laboratory
Source:Eurekalert

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