Acute lymphoblastic leukemia displays a distinct highly methylated genome (source data)
Creators
- Hetzel, Sara1
- Mattei, Alexandra L.1
- Kretzmer, Helene1
- Qu, Chunxu2
- Chen, Xiang3
- Fan, Yiping4
- Wu, Gang4
- Roberts, Kathryn G.2
- Luger, Selina5
- Litzow, Mark6
- Rowe, Jacob7
- Paietta, Elisabeth8
- Stock, Wendy9
- Mardis, Elaine R.10
- Wilson, Richard K.10
- Downing, James R.2
- Mullighan, Charles G.2
- Meissner, Alexander1
- 1. Department of Genome Regulation, Max Planck Institute for Molecular Genetics
- 2. Department of Pathology, St Jude Children's Research Hospital
- 3. Department of Computational Biology, St Jude Children's Research Hospital
- 4. Center for Applied Bioinformatics, St Jude Children's Research Hospital
- 5. Abramson Cancer Center, University of Pennsylvania
- 6. Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester
- 7. Department of Hematology, Shaare Zedek Medical Center
- 8. Department of Oncology, Montefiore Medical Center
- 9. University of Chicago Comprehensive Cancer Center
- 10. Institute for Genomic Medicine, Nationwide Children's Hospital
Description
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 (WGBS) of leukemic cells of multiple subtypes of ALL, leukemia cell lines and normal hematopoietic cells, and show that in contrast to most cancers, ALL samples 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 across patients that is influenced by TET2 and DNMT3B. These findings demonstrate a distinct methylome of ALL characterized by an unusually highly methylated genome, and provide important insights into the mechanisms underlying deregulation of methylation in cancer.
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