New insights into the genetic drivers of prostate cancer that may inform treatment decisions are highlighted in two papers published online in Nature and Nature Communications this week. Robert Bristow and colleagues present the largest prostate cancer whole-genome sequencing study reported to date in Nature, and publish an analysis of a uniquely aggressive form of prostate cancer in Nature Communications.
Prostate cancer is one the most common forms of cancer to be diagnosed in men, and around 30% of diagnosed men tend to relapse after treatment. Understanding the genetic factors that drive progression and aggression in this disease could help to identify distinct cancer sub-types and may lead to the development of new treatments. To identify such genetic drivers, Robert Bristow, Paul Boutros and colleagues analyse 200 whole-genome sequences of localized indolent prostate cancer tumours. The analysis highlights differences in mutational profiles between localized intermediate-risk prostate cancer and advanced metastatic, castration-resistant prostate cancer. These differences may provide a basis for selecting the appropriate lines of treatment in different cases, although the authors note that replication of the newly identified alterations and disease biomarkers in additional studies will be required.
In the second study, Bristow, Gail Risbridger and colleagues focus on the drivers of aggression in a subset of prostate cancer defined by mutations in the BRCA2 gene (a gene commonly implicated in breast cancer). They analyse the genomes of tumours from 14 patients with BRCA2-mutant prostate cancer and find alterations in genes that have previously been associated with metastatic disease; these alterations may be associated with the more aggressive nature of the tumours. This finding demonstrates the genetic basis of the more aggressive nature of BRCA2-mutant prostate cancer, and supports recommendations for intensified initial treatments.
Articles: Genomic hallmarks of localized, non-indolent prostate cancer, Robert G. Bristow et al., Nature, doi:10.1038/nature20788, published online 9 January 2017.
Germline BRCA2 mutations drive prostate cancers with distinct evolutionary trajectories, Robert G. Bristow et al., Nature Communications, doi:10.1038/ncomms13671, published online 9 January 2017.