![]() The presence of preCRCs precedes CRC onset by ~ 10 years, thereby providing a substantial time window for preventive interventions. ![]() These trends are largely attributable to the increasing use of population-based colonoscopy screening, which allows the identification and removal of early-stage CRCs as well as neoplastic lesions regarded as precancerous (preCRCs), such as conventional adenomas (cADNs) and sessile serrated lesions (SSLs). The past 40 years have witnessed considerable reductions in both the mortality and incidence of colorectal cancer (CRC). These validated DNA hypermethylation markers can be exploited to develop more accurate noninvasive colorectal tumor screening assays. From these, a selected candidate panel of 30 DMRs correctly identified 58/59 tumors (area under the receiver operating curve: 0.998). Strong statistical significance for the difference in methylation levels was observed across the full set of 990 investigated DMRs. Based on differential DNA methylation tests, a panel of candidate DMRs was chosen on a subset of our cohort and then validated on the remaining part of our cohort and two publicly available datasets with respect to their stratifying potential between preCRCs and normal mucosa. We used targeted bisulfite sequencing to validate these 990 potential biomarkers in 59 preCRC tissue samples (41 conventional adenomas, 18 sessile serrated lesions), each with a patient-matched normal mucosal sample. We have now conducted a study to validate 990 of these differentially methylated DNA regions (DMRs) in a new series of preCRCs. ![]() We previously identified 16,772 colorectal cancer-associated hypermethylated DNA regions that were also detectable in precancerous colorectal lesions (preCRCs) and unrelated to normal mucosal aging.
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