SETD2 and cancer: However, the impact of SETD2 loss of function on methylation has only been studied in a few cancers, namely renal, glioma, and GI stromal tumours [22, 26, 35, 37]. However, a pan-cancer analysis of the impact and functional characterisation of SETD2 loss and depletion on DNA methylation is lacking. To further explore the relationship between SETD2 status and DNA methylation profiles we used TCGA data to assess the impact of SETD2 mutation and copy number variation in 12 cancer types where SETD2 alterations were present in greater than 3% of the samples and methylation data was available.