Implications of Epigenetic Drift in Colorectal Neoplasia.

ABSTRACT: Many normal tissues undergo age-related drift in DNA methylation, providing a quantitative measure of tissue age. Here, we identify and validate 781 CpG islands (CGI) that undergo significant methylomic drift in 232 normal colorectal tissues and show that these CGI continue to drift in neoplasia while retaining significant correlations across samples. However, compared with normal colon, this drift advanced (∼3-4-fold) faster in neoplasia, consistent with increased cell proliferation during neoplastic progression. The observed drift patterns were broadly consistent with modeled adenoma-to-carcinoma sojourn time distributions from colorectal cancer incidence data. These results support the hypothesis that, beginning with the founder premalignant cell, cancer precursors frequently sojourn fo

SUBMITTER: Luebeck GE 

PROVIDER: S-EPMC6359943 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature