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In a bid to uncover mutations specific to metastatic castration-resistant prostate cancer that could inform treatment approaches, researchers led by the University of Michigan's Arul Chinnaiyan performed whole-exome and transcriptome sequencing on bone or soft tissue tumor biopsies collected from 150 people with mCRPC.

Mutations among the AR, ETS, TP53, and PTEN genes were common, they note in Cell this week, adding that TP53 and AR changes were enriched in mCRPC samples, as compared to primary prostate cancer. They also found new mutations within PIK3CA/B, R-spondin, BRAF/RAF1, APC, b-catenin, and ZBTB16/PLZF.

But Chinnaiyan and his colleagues also discovered that BRCA2, BRCA1, and ATM aberration occurred at higher frequencies among mCRPC than primary prostate cancers. The BRCA1 and BRCA2 mutations, generally associated with breast cancer risk, were present in some 15 percent of advanced prostate cancer cases.

The Wall Street Journal notes that these mutations had been observed previously in prostate cancer, though at lower frequencies. "We had no idea they were that common," study author Charles Sawyers from Memorial Sloan Kettering Cancer Center tells the Journal.

These alterations indicate that some mCRPC patients may benefit from PARP inhibitors, though the Journal notes that clinical trials will need to be conducted to confirm that.

Overall, Chinnaiyan, Sawyers, and their colleagues uncovered genetic aberrations in nearly 90 of the patients surveyed that appeared to be clinically actionable.

This finding indicates "patients with advanced prostate cancer should get some level of molecular profiling done" to better tailor their treatment, Chinnaiyan adds.