KSR2 and cancer: We found that those genes containing differentially modified 5hmC loci were enriched in several canonical pathways relevant to cancer pathobiology (Table S2) (p < 0.1, gene count > 5), such as PI3K-Akt signaling pathway (e.g., FGF9, PDGFA, and TCL1B), Rap1 signaling pathway (e.g., MRAS, IGF1R, and ADCY9), and Ras signaling pathway (e.g., KSR2, EGF, and CALM2); as well as GO biological processes, such as positive regulation of GTPase activity (e.g., SMAP2, GIT2, and RSU1) and fatty acid biosynthetic process (e.g., PRKAG1, ELOVL7, and SCD5) (Figure 3A) [23,24,25].