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Acute lymphoblastic leukemia displays a distinct highly methylated genome

ABSTRACT: DNA methylation is tightly regulated during development and is stably maintained in normal cells. In contrast, the methylome of cancer cells is commonly characterized by a global loss of DNA methylation co-occurring with CpG island hypermethylation. In acute lymphoblastic leukemia (ALL), the commonest childhood cancer, perturbations of CpG methylation have been reported to be associated with genetic disease subtype and outcome, but data examining large cohorts at genome-wide scale are lacking. Here, we performed whole-genome bisulfite sequencing of leukemic cells across multiple subtypes of ALL, leukemia cell lines and normal hematopoietic cells, and show that in contrast to most cancers, ALL samples only exhibit CpG island hypermethylation but minimal global loss of methylation. This was most pronounced in T-ALL and accompanied by an exceptionally broad range of hypermethylation of CpG islands between patients that is influenced by TET2 and DNMT3B. These findings demonstrate that ALL is characterized by an unusually highly methylated genome, and provide insights into the deregulation of methylation in cancer.

ORGANISM(S): Homo sapiens

PROVIDER: GSE164040 | GEO | 2022/03/03

REPOSITORIES: GEO

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