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Nat Immunol. 2015 Jun;16(6):653-62. doi: 10.1038/ni.3148. Epub 2015 Apr 13.

TET1 is a tumor suppressor of hematopoietic malignancy.

Author information

1
1] Howard Hughes Medical Institute and Department of Pathology, NYU School of Medicine, New York, New York, USA. [2] NYU Cancer Institute and Helen L. and Martin S. Kimmel Center for Stem Cell Biology, NYU School of Medicine, New York, New York, USA.
2
1] Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA. [2] Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
3
Department of Hemato-Oncology, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, New York, USA.
4
Department of Medicine, Weill Cornell Medical College, Cornell University, New York, New York, USA.
5
Department of Laboratory Medicine, University of California San Francisco, San Francisco, California, USA.
6
Howard Hughes Medical Institute and Department of Pathology, NYU School of Medicine, New York, New York, USA.
7
Center for Health Informatics and Bioinformatics, NYU School of Medicine, New York, New York, USA.

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.

PMID:
25867473
PMCID:
PMC4545281
DOI:
10.1038/ni.3148
[Indexed for MEDLINE]
Free PMC Article

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