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Analysis of DNA methylation in normal B cells and chronic lymphocytic leukemia

Charting differences between tumors and normal tissue is a mainstay of cancer research. However, clonal tumor expansion from complex normal tissue architectures potentially obscures cancer-specific events, including divergent epigenetic patterns. Using whole-genome bisulfite sequencing of normal B cell subsets, we observed broad epigenetic programming of selective transcription factor binding sites coincident with the degree of B cell maturation. By comparing normal B cells to malignant B cells from 268 patients with chronic lymphocytic leukemia (CLL), we showed that tumors derive largely from a continuum of maturation states reflected in normal developmental stages. Epigenetic maturation in CLL was associated with an indolent gene expression pattern and increasingly favorable clinical outcomes.As second study using these samples focued on evolution and resulting intra-tumor heterogeneity in CLL. We used 450k bead-chip arrays to study DNA methylomes in 68 chronic lymphocytic leukemia (CLL) cases, including 28 serial cases. The result establishs linked evolution of epigenetic and genetic alterations in progressive disease, revealing an important aspect of the biology of epigenetics in cancer.

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID Description Technology Samples
EGAD00001001675 Illumina HiSeq 2000 42
EGAD00001001676 Illumina HiSeq 2000 12
EGAD00010000871 226
Publications Citations
Evolution of DNA methylation is linked to genetic aberrations in chronic lymphocytic leukemia.
Cancer Discov 4: 2014 348-361
DNA methylation dynamics during B cell maturation underlie a continuum of disease phenotypes in chronic lymphocytic leukemia.
Nat Genet 48: 2016 253-264
Sex-related DNA methylation differences in B cell chronic lymphocytic leukemia.
Biol Sex Differ 10: 2019 2
Genome-wide promoter methylation of hairy cell leukemia.
Blood Adv 3: 2019 384-396
The proliferative history shapes the DNA methylome of B-cell tumors and predicts clinical outcome.
Nat Cancer 1: 2020 1066-1081
A leukemia-protective germline variant mediates chromatin module formation via transcription factor nucleation.
Nat Commun 13: 2022 2042
Genome-wide DNA methylation profiling in chronic lymphocytic leukaemia.
Front Genet 13: 2022 1056043