New study reveals 11 gene mutations linked to aggressive prostate cancer

NEW YORK: Scientists have identified mutations in 11 genes associated with aggressive forms of prostate cancer

The findings led by a team at the University of Southern California (USC) come from the largest-scale prostate cancer study-ever exploring the exome -- the key sections of the genetic code that contain the instructions to make proteins.

For the study, scientists analysed samples from about 17,500 prostate cancer patients.

The study, published in JAMA Oncology journal also uncovered mutations associated with higher risk for more-aggressive, deadlier prostate cancer that are not currently included on genetic test panels.

The researchers also found some genes that are currently part of such panels are not linked with risk for aggressive disease.

"Very large studies are needed to inform the creation of gene panels used for testing," said Christopher Haiman, corresponding author, Professor of Population and Public Health Sciences at the USC's Keck School of Medicine.

"Some of the genes in these panels were based on small studies and were not associated with prostate cancer in our study. We also found evidence that other genes perhaps ought to be added.

"The results aren't completely definitive, but it's clear that more work needs to be done to determine which genes oncologists should focus on in testing," Haiman added.

The team combined information from 18 studies conducted in the US, Europe and Australia and analysed blood samples from prostate cancer patients of European descent, 9,185 of whom had aggressive disease and 8,361 who did not and compared the frequency of mutations among the two groups.

In the first stage, they sequenced the entire set of protein-coding genes among almost a third of participants and in the second stage, the researchers used samples from the remaining participants to zoom in on a subset of 1,749 genes that either had previously been associated with cancer or showed up as likely candidates in the first phase.

That subset included almost 200 genes involved with DNA repair. When that process is disrupted, it creates an opportunity for cancerous cells to arise and take hold.

"This suggests that mutations in these people may put them at greater risk for their cancer later becoming more advanced," said Haiman.