SETD2 and neoplasm: Thus, loss of Vhl in mice still leaves functional Pbrm1, Bap1, and Setd2 genes, while loss of chromosome 3p, which is the typical first-hit event in humans, often causes loss of PBRM1, BAP1 and, SETD2, predisposing humans to additional second-hit inactivating mutations in these genes and subsequent tumor development (107).