We provide supporting evidence to suggest that PCGT methylation, as exemplified here by HAND2 DNAme (the hub of the top-ranked EpiMod hotspot), is not merely a passive epigenetic feature of cancer but plays a functional role that facilitates the carcinogenic process—i.e., in the development of endometrial premalignancy (CAH). Here, HAND2 is linked to congenital adrenal hyperplasia.