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  Acute lymphoblastic leukemia displays a distinct highly methylated genome

Hetzel, S., Mattei, A. L., Kretzmer, H., Qu, C., Chen, X., Fan, Y., et al. (2022). Acute lymphoblastic leukemia displays a distinct highly methylated genome. Nature Cancer, 2022. doi:10.1038/s43018-022-00370-5.

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NatureCancer_Hetzel et al_2022.pdf (Publisher version), 16MB
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Hetzel, Sara1, Author              
Mattei, Alexandra L.1, Author              
Kretzmer, Helene1, Author              
Qu, Chunxu, Author
Chen, Xiang , Author
Fan, Yiping , Author
Wu, Gang, Author
Roberts, Kathryn G. , Author
Luger, Selina , Author
Litzow, Mark, Author
Rowe, Jacob, Author
Paietta, Elisabeth , Author
Stock, Wendy, Author
Mardis, Elaine R. , Author
Wilson, Richard K. , Author
Downing, James R. , Author
Mullighan, Charles G., Author
Meissner, Alexander1, Author              
Affiliations:
1Dept. of Genome Regulation (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_2379694              

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 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.

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Language(s): eng - English
 Dates: 2022-03-252022-05-19
 Publication Status: Published online
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 Rev. Type: -
 Identifiers: DOI: 10.1038/s43018-022-00370-5
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Title: Nature Cancer
Source Genre: Journal
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Publ. Info: New York, NY : Springer Nature
Pages: - Volume / Issue: 2022 Sequence Number: - Start / End Page: - Identifier: ISSN: 2662-1347 (online)