VHL and nonpapillary renal cell carcinoma: To identify genes that maintain the dependency of ccRCC cells on PAX8, we performed loss-of-function screening on a PAX8 knockdown (KD) background in 786-M1A cells, a metastatic VHL mutant ccRCC cell line,17 using a single guide RNA (sgRNA) library targeting chromatin regulators,18 key factors involved in the maintenance of cellular identity (Figure 1A).