TET1 is a tumor suppressor of hematopoietic malignancy
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Jaenisch_Tet1 is a tumor.pdf
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Author(s)
Cimmino, Luisa
Ndiaye-Lobry, Delphine
Yap, Yoon Sing
Bakogianni, Sofia
Yu, Yiting
Bhattacharyya, Sanchari
Shaknovich, Rita
Geng, Huimin
Lobry, Camille
Mullenders, Jasper
Date Issued
April 2015
Journal
Nature Immunology
Publisher
Nature Publishing Group
Citation
Cimmino, Luisa et al. “TET1 Is a Tumor Suppressor of Hematopoietic Malignancy.” Nature Immunology 16.6 (2015): 653–662.
Version
Author's final manuscript
Abstract
The methylcytosine dioxygenase TET1 (‘ten-eleven translocation 1’) is an important regulator of 5-hydroxymethylcytosine (5hmC) in embryonic stem cells. The diminished expression of TET proteins and loss of 5hmC in many tumors suggests a critical role for the maintenance of this epigenetic modification. Here we found that deletion of Tet1 promoted the development of B cell lymphoma in mice. TET1 was required for maintenance of the normal abundance and distribution of 5hmC, which prevented hypermethylation of DNA, and for regulation of the B cell lineage and of genes encoding molecules involved in chromosome maintenance and DNA repair. Whole-exome sequencing of TET1-deficient tumors revealed mutations frequently found in non-Hodgkin B cell lymphoma (B-NHL), in which TET1 was hypermethylated and transcriptionally silenced. Our findings provide in vivo evidence of a function for TET1 as a tumor suppressor of hematopoietic malignancy.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1038/ni.3148
