EGAGenomicsIllumina HiSeq 2000;https://ega-archive.org/datasets/EGAD0000100167542EGA dataset EGAD00001001675EGAAlthough clonal selection by genetic driver aberrations in cancer is well documented, the ability of epigenetic alterations to promote tumor evolution is undefined. We used 450k arrays and next-generation sequencing to evaluate intratumor heterogeneity and evolution of DNA methylation and genetic aberrations in chronic lymphocytic leukemia (CLL). CLL cases exhibit vast interpatient differences in intratumor methylation heterogeneity, with genetically clonal cases maintaining low methylation heterogeneity and up to 10% of total CpGs in a monoallelically methylated state. Increasing methylation heterogeneity correlates with advanced genetic subclonal complexity. Selection of novel DNA methylation patterns is observed only in cases that undergo genetic evolution, and independent genetic evolution is uncommon and is restricted to low-risk alterations. These results reveal that although evolution of DNA methylation occurs in high-risk, clinically progressive cases, positive selection of novel methylation patterns entails coevolution of genetic alteration(s) in CLL.Evolution of DNA methylation is linked to genetic aberrations in chronic lymphocytic leukemia.Oakes Christopher C CC, Claus Rainer R, Gu Lei L, Assenov Yassen Y, Hüllein Jennifer J, Zucknick Manuela M, Bieg Matthias M, Brocks David D, Bogatyrova Olga O, Schmidt Christopher R CR, Rassenti Laura L, Kipps Thomas J TJ, Mertens Daniel D, Lichter Peter P, Döhner Hartmut H, Stilgenbauer Stephan S, Byrd John C JC, Zenz Thorsten T, Plass Christoph Cfalseena-DATASET-DKFZ-Epigenomics-19-11-2015-09:37:32:058-207 - samplesRNA-seq of peripheral blood samples from CLL patients.2017-07-26 15:39:26EGAD00001001675960624356097EGAC00001000279EGAS00001000534