Year: 2022
Type: article
Study design: Observational Study
Abstract: DNA methylation is tightly regulated during development and is stably maintained in healthy cells. In contrast, cancer cells are 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 from large cohorts at a genome-wide scale are lacking. Here, we performed whole-genome bisulfite sequencing across ALL subtypes, leukemia cell lines and healthy hematopoietic cells, and show that unlike most cancers, ALL samples exhibit CpG island hypermethylation but minimal global loss of methylation. This was most pronounced in T cell ALL and accompanied by an exceptionally broad range of hypermethylation of CpG islands between patients, which is influenced by TET2 and DNMT3B. These findings demonstrate that ALL is characterized by an unusually highly methylated genome and provide further insights into the non-canonical regulation of methylation in cancer.
Source: Nature Cancer
Institutions: Max Planck Institute for Molecular Genetics, Harvard University, St. Jude Children's Research Hospital, Abramson Cancer Center, University of Pennsylvania, Mayo Clinic, Shaare Zedek Medical Center, Bikur Cholim Hospital, Montefiore Medical Center, University of Chicago, University of Chicago Medicine Comprehensive Cancer Center, Nationwide Children's Hospital, Broad Institute, Freie Universität Berlin
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $11,390
Awards: G1062975487, G169511485, ECOG-ACRIN Network Group Operations Center, A BLUEPRINT of Haematopoietic Epigenomes, G2954099590, G3207356259, G393177772, G4129138430, G4766096375, G4869702982, G5417201949, G5702163051, G6289520395, Translating genomic discoveries to improved outcomes for high risk acute leukemia, Cancer Center Support Grant (CCSG)
OpenAlex ID: W4280602103