The proliferative history shapes the DNA methylome of B-cell tumors and predicts clinical outcome.

ABSTRACT: We report a systematic analysis of the DNA methylation variability in 1,595 samples of normal cell subpopulations and 14 tumor subtypes spanning the entire human B-cell lineage. Differential methylation among tumor entities relates to differences in cellular origin and to de novo epigenetic alterations, which allowed us to build an accurate machine learning-based diagnostic algorithm. We identify extensive patient-specific methylation variability in silenced chromatin associated with the proliferative history of normal and neoplastic B cells. Mitotic activity generally leaves both hyper- and hypomethylation imprints, but some B-cell neoplasms preferentially gain or lose DNA methylation. Subsequently, we construct a DNA methylation-based mitotic clock called epiCMIT, whose lapse magn

SUBMITTER: Duran-Ferrer M 

PROVIDER: S-EPMC8168619 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature