Re: Inherited DNA-Repair Gene Mutations in Men with Metastatic Prostate Cancer.

Experts’ summary: In this paper, Pritchard and colleagues tried to ascertain the spectrum and prevalence of germ-line DNA repair gene mutations in metastatic prostate cancer (PCa) by next-generation sequencing. They enrolled a total of 692 patients with metastatic PCa; no selection was based on family history, age, or any knowledge of genetic background. Of the 692 men evaluated, 82 (11.8%) had at least one germ-line mutation in a gene involved in DNA repair processes. Mutations were identified in 16 different genes; BRCA2 was the gene most frequently involved (44% of total mutations). When information regarding family history and age were obtained, mutation did not differ significantly. Finally, the authors compared the frequency of germ-line DNA repair gene mutations among men with metastatic PCa with the frequency of such mutations among men with localised PCa. The odds of DNA repair gene mutations being present among men with metastatic PCa differed significantly from the odds among men with localised lowto intermediate-risk tumours (odds ratio [OR]: 5.3; 95% confidence interval [CI], 1.9–20.2; p < 0.001) and among those with high-risk tumours (OR: 2.2; 95% CI, 1.3–4.0; p = 0.002). In summary, the incidence of germ-line mutations in genes mediating DNA repair processes among men with metastatic PCa was 11.8%, which was significantly higher than the incidence among men with localised PCa. The frequencies of germ-line mutations in DNA repair genes among men with metastatic disease did not differ significantly according to age at diagnosis or family history of PCa.