A germline mutation in PBRM1 predisposes to renal cell carcinoma

Many cases of familial renal cell carcinoma (RCC) are unexplained by mutations in known predisposing genes or shared environmental factors. We have shown that PBRM1, a tumor supressor gene with frequent somatic mutations in clear cell RCC, is also a RCC susceptibility gene. Indeed, four members from the same family, all with a history of RCC, carried the same germline pathogenic mutation in PBRM1, whereas an unaffected relative did not. Complementary analyses supported our findings as there was loss of the wild-type allele and absence of expression of the normal protein in tumoral tissue extracted from the patients RCCs. (By Patrick R Benusiglio, http://jmg.bmj.com/content/early/2015/04/23/jmedgenet-2014-102912 )