Germline mutations in ribonuclease gene linked to prostate cancer

By Will Boggs, MD

NEW YORK (Reuters Health) – In some cases of hereditary prostate cancer, the cause may be attributable to germline mutations in the ribonuclease L gene (RNASEL), according to a report in the February issue of Nature Genetics published online January 22.

Dr. Jeffrey Trent, from the National Human Genome Research Institute in Bethesda, Maryland, and colleagues investigated the known prostate susceptibility locus on chromosome 1 (HPC1) in 26 families with hereditary prostate cancer.

"We identified RNASEL by a positional cloning/candidate gene method, and show that a nonsense mutation and a mutation in an initiation codon of RNASEL segregate independently in two HPC1-linked families," the investigators report.

In contrast, RNASEL mutations were rare in individuals from control populations (1 in 144 normal controls) or from individuals with non-familial prostate cancer (2 in 258), the researchers note.

The authors speculate that the loss of RNASEL's tumor suppressor function disrupts the critical balance between hormonally regulated growth and cell death, shifting "this balance toward cell growth, creating a favorable environment for the development of prostate cancer."

"I think the most interesting part clinically is the finding (preliminary but interesting) that all of the men in our study who had a mutation in RNASEL that inactivated the protein had clinically significant disease," Dr. Trent told Reuters Health. "The point being, it is possible this gene will play some role in the clinical course of the disease (accelerating it) and may 'target' men likely to have advanced disease."

"Many groups are already at work attempting to define the fraction of hereditary prostate cancer cases which show a change in the RNASEL gene," Dr. Trent added. "If this finding is similar to others in this era of finding 'modifier' genes, then it will take a large effort to provide definitive evidence."

"These findings could be significant," the authors conclude, "as the identification of germline mutations in this gene could lead to early diagnosis and therapeutic approaches for prostate cancer cases linked to HPC1."

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