Possible Prostate Cancer Gene Found

23 January 2002 (All day)

Cancer risk? A gene linked to prostate cancer suggests that cells without the enzyme RNase L (stained brownish red, left arrow) are more likely to turn cancerous than those with it (right arrow).

Researchers have identified a gene that may cause some cases of inherited prostate cancer. They have also proposed the first mechanism for how prostate cancer might arise from the mutations in the gene, which is best known for defending cells against viruses. Although only about 10% of prostate cancer victims inherit the disease, the genetic culprit could reveal broader clues about how prostate cancer wreaks its damage.

The gene is located on chromosome 1, an area that's been scrutinized for prostate cancer genes since 1996, when family studies revealed a link between a region of that chromosome and the disease (ScienceNOW, 21 November 1996). Although geneticists had pinpointed locations on chromosomes 1, 17, 20, and X linked to the disease, disease-causing genes within these regions had remained elusive. One gene in the critical region of chromosome 1 encodes an enzyme called RNase L; the L stands for latent because in healthy cells the enzyme lies dormant. It springs to life in the presence of double-stranded RNA, which often accompanies invasion of the cell by a virus. Adding RNase L to a cell triggers cell suicide, suggesting the enzyme may prevent viruses from spreading, and may help suppress tumors by preventing cells from multiplying out of control. But this role has remained speculative and has been contradicted by studies showing that mice without RNase L do not develop tumors.

An international research collaboration involving 14 institutions has now published evidence that a lack of RNase L may cause prostate cancer. After screening DNA samples from 26 prostate cancer patients and their families, all at high-risk for the disease, they found mutations in the RNase L gene in two families. Individuals with prostate cancer had inherited only one good copy of the gene. At some point, a mutation had disabled the good copy in a prostate cell. Cell-staining revealed that the tumor cells contained no functional RNase L, the group reports in the February issue of Nature Genetics. The researchers believe that this lack triggered the tumor growth.

"It's not going to be the end all and be all--it may be one of many," says cancer researcher Kimberly Rieger-Christ of the Lahey Clinic in Burlington, Massachusetts. Rieger notes that mutations in RNase L might work in concert with other mutations to cause the disease, which could explain why mice lacking RNase L don't develop cancer.

Related sites
List of authors available at Nature Genetics
Prostate cancer information, from NCI
Sciencepaper reporting discovery of HPC1 locus, 1996

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