Our study expands these findings by highlighting the prevalence of somatic LOY among men affected by ccRCC, and suggesting a functional relevance for this aberration through down-regulation of previously unrecognized epigenetic modifiers KDM5D and KDM6C. Given the functional similarities between these genes and their X-linked homologs, it is plausible that down-regulation of KDM5D and KDM6C, through somatic LOY, may contribute to ccRCC development or progression. Here, KDM5D is linked to nonpapillary renal cell carcinoma.