Besides VHL, other genetic alterations in subgroup-5 involve the mutation of the chromatin remodeling gene PBRM1, the mutation of the histone methyltransferase gene SETD2, which has been identified as a tumor suppressor in KIRC [20] and high methylation rate of GSTP1 (Fig. 4 and in Additional file 1: Figure S8). Here, VHL is linked to neoplasm.