DNA mismatch repair (MMR) is suppressed in ccRCC by several ways: (1) The regulation of histone deacetylase HDAC6 by VHL gene deletion and ubiquitin-proteasome dependent MSH2 degradation (Dere et al., 2015; Zhang et al., 2014); (2) the haploid dose deficiency of MLH1 caused by deletion of chromosome 3p fragment (Wang et al., 2012); (3) the weakened MSH6 recruitment and transcriptional coupled repair by H3K36me3 depletion, which acts as a recognition target (Jonasch, Walker & Rathmell, 2021; Li et al., 2013). Here, VHL is linked to nonpapillary renal cell carcinoma.