Acute lymphoblastic leukemia displays a distinct highly methylated genome.
Journal
Nature cancer
ISSN: 2662-1347
Titre abrégé: Nat Cancer
Pays: England
ID NLM: 101761119
Informations de publication
Date de publication:
06 2022
06 2022
Historique:
received:
18
05
2021
accepted:
25
03
2022
pubmed:
20
5
2022
medline:
30
6
2022
entrez:
19
5
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 35590059
doi: 10.1038/s43018-022-00370-5
pii: 10.1038/s43018-022-00370-5
pmc: PMC9236905
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
768-782Subventions
Organisme : NCI NIH HHS
ID : P30 CA021765
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA197695
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA196172
Pays : United States
Informations de copyright
© 2022. The Author(s).
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