Substantial batch effects in TCGA exome sequences undermine pan-cancer analysis of germline variants.

TCGA germline data is exposed to strong batch effects with substantial variabilities among TCGA sequencing centers. We claim that those batch effects are consequential for numerous TCGA pan-cancer studies. In particular, these effects may compromise the reliability and the potency to detect new cancer predisposition genes. Furthermore, interpretation of pan-cancer analyses should be revisited in view of the source of the genomic data after accounting for the reported batch effects.