Notably, a 2015 exome study of HDGC (diffuse GC) families identified a germline variant in DOT1L, a histone methyltransferase, as a candidate predisposition gene Donner et al. found a DOT1L missense variant (p.Pro1146Leu) in a CDH1-negative diffuse GC family, raising the possibility that altered H3K79 methylation could predispose to gastric tumorigenesis [34]. Here, DOT1L is linked to gastric cancer.