A comparison of epigenetic mitotic-like clocks for cancer risk prediction.

ABSTRACT:

Background

DNA methylation changes that accrue in the stem cell pool of an adult tissue in line with the cumulative number of cell divisions may contribute to the observed variation in cancer risk among tissues and individuals. Thus, the construction of epigenetic "mitotic" clocks that can measure the lifetime number of stem cell divisions is of paramount interest.

Methods

Building upon a dynamic model of DNA methylation gain in unmethylated CpG-rich regions, we here derive a novel mitotic clock ("epiTOC2") that can directly estimate the cumulative number of stem cell divisions in a tissue. We compare epiTOC2 to a different mitotic model, based on hypomethylation at solo-WCGW sites ("HypoClock"), in terms of their ability to measure mitotic age of normal adult tissues and pr

SUBMITTER: Teschendorff AE 

PROVIDER: S-EPMC7315560 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature