DNA Methylation Profiling at Base-Pair Resolution Reveals Unique Epigenetic Features of Early-Onset Colorectal Cancer in Underrepresented Populations

Background. The incidence of early-onset colorectal cancer (EOCRC) has been rising at an alarming rate in the United States, and EOCRC disproportionately affects racial/ethnic minorities. Here, we construct comprehensive profiles of EOCRC DNA methylomes at base-pair resolution for a cohort of Hispanic and African American patients. Results. We show the epigenetic landscape of these EOCRC patients differs from that of late-onset colorectal cancer (LOCRC) patients, and methylation canyons in EOCRC tumor tissue preferentially overlapped genes in cancer-related pathways. Furthermore, we identify epigenetic alterations in metabolic genes that are specific to our racial/ethnic minority EOCRC cohort but not Caucasian patients from TCGA. Top genes differentially methylated between these cohorts included the obesity-protective MFAP2 gene as well as cancer risk susceptibility genes APOL3 and RNASEL. Conclusions. In this study, we provide to the scientific community high-resolution DNA methylomes for a cohort of EOCRC patients from underrepresented populations. Our exploratory findings in this cohort highlight epigenetic mechanisms underlying the pathogenesis of EOCRC and nominate novel biomarkers for EOCRC in underrepresented populations. Overall design: Whole-genome bisulfite sequencing of microdissected early-onset colorectal cancer tumors and normal adjacent colonic mucosal tissue from FFPE preserved tissues.