Acute lymphoblastic leukemia displays a distinct highly methylated genome
| Autor: | Sara Hetzel, Alexandra L. Mattei, Helene Kretzmer, Chunxu Qu, Xiang Chen, Yiping Fan, Gang Wu, Kathryn G. Roberts, Selina Luger, Mark Litzow, Jacob Rowe, Elisabeth Paietta, Wendy Stock, Elaine R. Mardis, Richard K. Wilson, James R. Downing, Charles G. Mullighan, Alexander Meissner |
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| Rok vydání: | 2022 |
| Předmět: |
Haematological cancer
Cancer Research Genome Human 500 Naturwissenschaften und Mathematik::570 Biowissenschaften Biologie::570 Biowissenschaften Biologie DNA Methylation Precursor Cell Lymphoblastic Leukemia-Lymphoma Precursor T-Cell Lymphoblastic Leukemia-Lymphoma Cancer epigenetics Oncology Cancer genomics Humans CpG Islands Child Promoter Regions Genetic Cancer |
| Zdroj: | Nature Cancer |
| ISSN: | 2662-1347 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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