KDM5C and KDM5D mutations have different consequences in clear cell renal cell carcinoma cells.

ABSTRACT: KDM5C is commonly mutated in clear cell renal cell carcinomas (ccRCC) in men but rarely in women. Introducing KDM5C mutation into two male and two female KDM5C wild-type ccRCC cell lines caused different phenotypes and non-overlapping transcriptional consequences, indicative of context-dependent functions of KDM5C. We identify that loss of the Y chromosome, harbouring the KDM5C homologue KDM5D, occurs in most male KDM5C mutant ccRCCs. Mutation of KDM5D in male 786-O cells prevented xenograft tumour formation and this phenotype was unexpectedly rescued by co-mutation of KDM5C, consistent with the co-occurrence of KDM5C mutation and loss of the Y chromosome in ccRCC. Transcriptional analyses showed that KDM5C and KDM5D regulate the expression of both overlapping as well as distinct sets of g

SUBMITTER: Muller M 

PROVIDER: S-EPMC11830100 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature