VHL and nonpapillary renal cell carcinoma: Previous studies have identified the somatic von Hippel-Lindau (VHL) mutations and downstream hypoxia-inducible factors (HIFs) - related pathways in the carcinogenesis of ccRCC, while recent high-throughput sequencing also identifies aberrant changes in epigenetic regulatory genes or precursor mRNA (pre-mRNA) splicing [2].