In one study, the DNA methylation changes were found in genes associated with control of metastasis (AOX-114 and RARB215), angiogenesis (RERG16 and ADAMTS917), and autoimmunity (IRF4 and FOXE-1).108 Hypermutation of FOXE-1 had been earlier reported to be a predictive biomarker of CRC in biopsies obtained by colonoscopy.109 In another study, hypermutated promoter regions of a panel of 30 CRC-associated genes was assayed in circulating DNA and proposed to be a biomarker of CRC.110 To what extent these blood markers are derived from circulating tumor cells, versus PBMC, is yet to be determined. Here, IRF4 is linked to colorectal carcinoma.