Understanding the genetic basis of prostate cancer

Genetic mutations in prostate cancer, the second most common cancer in men, are reported in two independent studies published inNature and Nature Genetics this week. The findings provide information that may help us to understand how specific genetic landscapes underlie disease progression and response to therapy. Both studies used a technique called exome sequencing (selective sequencing of the coding regions of the genome) to identify these mutations.

Levi Garraway and colleagues report in Nature Genetics the exome sequencing of 112 prostate cancer tumour and matched normal samples. They identify recurrent mutations in multiple genes in prostate cancer. The SPOP gene contained the most frequent recurrent mutations, present in 6-15% of tumours, and may define a new subtype of prostate cancers.

In theNature paper, Arul Chinnaiyan and co-workers analyse autopsy samples from 61 patients with treated and non-treated metastatic castration-resistant prostate cancer to investigate the role of mutations in this lethal disease subtype. Progression to this subtype occurs following heavy treatment with androgen deprivation therapy — ‘chemical castration’ — which reduces the effects of androgen hormones, on which many prostate cancers depend. The authors find a small number of mutations including in the genes affecting androgen receptors. The newly identified mutations reveal a novel mechanism that underlies deregulation of androgen signalling in prostate cancer. This is turn identifies a potential resistance mechanism to anti-androgen therapies.