Clear-cell renal cell carcinoma exhibits unique molecular features, some of which are associated with the response to immunotherapy. However, the interactions between different genomic entities remains incompletely understood. In this issue, Zhou and colleagues show that PBRM1 inactivation is associated with increased expression of specific human endogenous retroviruses and identify HIF1/2A transcriptional activity as an important mediator of this interaction, helping uncover the interplay between some of the key molecular traits of this disease. See related article by Zhou et al., p. 285 (3).
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