@article{335fe6232c764ae4bb993c7b5c5de955,
title = "Acute lymphoblastic leukemia displays a distinct highly methylated genome",
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.",
author = "Sara Hetzel and Mattei, {Alexandra L.} and Helene Kretzmer and Chunxu Qu and Xiang Chen and Yiping Fan and Gang Wu and Roberts, {Kathryn G.} and Selina Luger and Mark Litzow and Jacob Rowe and Elisabeth Paietta and Wendy Stock and Mardis, {Elaine R.} and Wilson, {Richard K.} and Downing, {James R.} and Mullighan, {Charles G.} and Alexander Meissner",
note = "Funding Information: We thank A. Bolondi, J. Batki, L. Haut, P. Guckelberger and other members of the Meissner laboratory, T. Risch, L. Barros de Andrade e Sousa and V. Stanislas for discussions and advice. We thank S. Otto for assistance with verifying knockout cell lines, the MPIMG Flow Cytometry Facility for assistance sorting cells and the MPIMG Sequencing Core Facility, in particular S. Klages and B. Timmermann. This work was supported by the American Lebanese Syrian Associated Charities of St. Jude Children{\textquoteright}s Research Hospital. C.G.M. is supported by a National Cancer Institute Outstanding Investigator Award (R35 CA197695) and Cancer Center Core Support Grant CA021765, the St. Jude Children{\textquoteright}s Research Hospital - Washington University Pediatric Cancer Genome Project, and the St. Jude Children{\textquoteright}s Research Hospital Collaborative Research Consortium on Chromatin Regulation in Pediatric Cancer. A.M. is supported by the Max Planck Society. Funding Information: This study makes use of data generated by the Blueprint Consortium. A full list of the investigators who contributed to the generation of the data is available from www.blueprint-epigenome.eu . Funding for the Blueprint project was provided by the European Union{\textquoteright}s Seventh Framework Programme (FP7/2007–2013) under grant agreement no. 282510 Blueprint. The results shown here are in part based upon data generated by the TCGA Research Network: https://www.cancer.gov/tcga . Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = jun,
doi = "10.1038/s43018-022-00370-5",
language = "English (US)",
volume = "3",
pages = "768--782",
journal = "Nature Cancer",
issn = "2662-1347",
publisher = "Nature Research",
number = "6",
}
