Patients with a harmful variant of the gene RB1 were almost seven times as likely to relapse after treatment with standard chemotherapy, as well as having a threefold higher risk of death overall.
'We identified one particular genetic mutation that seems to indicate that tumours are going to be very aggressive, and that the affected men need the most intensive treatment we have available,' said Johann de Bono, Regius professor of cancer research at the Institute of Cancer Research (ICR), and an author of the study.
The team investigated 444 tumour samples from 429 men with advanced prostate cancer by sequencing the DNA and measuring the activity of genes and the features of the tumour tissue. The gene that stood out most in terms of survival and reaction to treatment was the RB1 gene.
Other genetic mutations with potential therapeutic applications were also discovered, including mutations in the gene p53 and an androgen receptor gene, which were associated with an increased likelihood of relapse after standard chemotherapy. Mutations in the DNA repair genes BRCA1 and BRCA2, among others, were found to be relatively common among advanced prostate cancer patients, but had no apparent effect on treatment or survival rates.
The researchers hope that the findings could lead to a screening programme in patients to determine whether they might benefit from more intensive treatment. It could also be the starting point for the development of a targeted therapy for advanced prostate cancer with an RB1 mutation.
Professor Paul Workman, chief executive of the ICR, said: 'The crucial thing now is that we make use of this information, by developing a test to identify affected men and to make sure they receive the best treatments we have available today, while also focusing our efforts on improving options for the future.'
The study was published in the journal PNAS.