Consistent with our prior observations, we found that somatic loss-of-function mutations in MSH2 and MSH6 were the primary cause of microsatellite instability in patients with prostate cancer [13].This is in contrast to colorectal cancer where hypermutation has been found to be associated with epigenetic silencing of MLH1, which occurs in nearly 2/3 of the cases [21]. Here, MSH6 is linked to prostate carcinoma.