Locally disordered methylation forms the basis of intratumor methylome variation in chronic lymphocytic leukemia.

ABSTRACT: Intratumoral heterogeneity plays a critical role in tumor evolution. To define the contribution of DNA methylation to heterogeneity within tumors, we performed genome-scale bisulfite sequencing of 104 primary chronic lymphocytic leukemias (CLLs). Compared with 26 normal B cell samples, CLLs consistently displayed higher intrasample variability of DNA methylation patterns across the genome, which appears to arise from stochastically disordered methylation in malignant cells. Transcriptome analysis of bulk and single CLL cells revealed that methylation disorder was linked to low-level expression. Disordered methylation was further associated with adverse clinical outcome. We therefore propose that disordered methylation plays a similar role to that of genetic instability, enhancing the abili

SUBMITTER: Landau DA 

PROVIDER: S-EPMC4302418 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature