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Study identifies new treatment target in BRCA2-mutant prostate cancer

Genetic abnormalities associated with poor prognosis in prostate cancer are particularly common in men with germline mutations in the BRCA2 gene, a new study reports.

The new research suggests men with inherited BRCA2 mutations may be at increased risk of accumulating additional dangerous mutations within their tumours, and could explain why their cancers tend to be unusually aggressive.

The study, published in the Annals of Oncology, has identified one particular genetic abnormality that is common in the tumours of BRCA2-mutation carriers, and could be a new treatment target in these cancers.

Scientists at The Institute of Cancer Research, London, collaborated with scientists at the Spanish National Cancer Research Centre, Madrid, to identify the genetic abnormalities present in the prostate tumours of patients with BRCA2 germline mutations. They assessed the frequency with which mutations occurred compared with the tumours of men who were not BRCA2 carriers.

The study found that patients who carry germline BRCA2 mutations harbour significantly more copy-number alterations than those who do not have germline mutations. In particular, patients with BRCA2 mutations were more likely to have extra copies of a gene called c-MYC – potentially leading to uncontrolled cell growth.

Targeting c-MYC could therefore be a potential treatment for patients with the BRCA2 mutation.

The researchers profiled DNA from prostate cancer and healthy tissue in 20 men who carried BRCA2 germline mutations, and 40 who did not. They were enrolled in the UK Genetics Prostate Cancer Study (UKGPCS), EMBRACE (Epidemiological Study of Familial Breast Cancer) and the IMPACT study.

Professor Ros Eeles, Professor of Oncogenetics at The Institute of Cancer Research, London, and honorary consultant at The Royal Marsden NHS Foundation Trust, said: “Men with BRCA2 mutations tend to have more aggressive prostate cancers than those who don’t, and our new study finds a potential reason in the genetic abnormalities within these tumours.

“Detailing the genetic mutations within the tumours of BRCA2-mutation carriers allows us to start identifying new treatment targets, and devising new personalised treatment strategies. We believe a first step could be to target c-MYC, since we’ve provided evidence that this is often present in increased copy numbers in BRCA-mutant cancers.”

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