2. Academic Validation
  3. TET1 is a tumor suppressor of hematopoietic malignancy

TET1 is a tumor suppressor of hematopoietic malignancy

  • Nat Immunol. 2015 Jun;16(6):653-62. doi: 10.1038/ni.3148.
Luisa Cimmino 1,  Meelad M Dawlaty 2,  Delphine Ndiaye-Lobry 1,  Yoon Sing Yap 1,  Sofia Bakogianni 1,  Yiting Yu 3,  Sanchari Bhattacharyya 3,  Rita Shaknovich 4,  Huimin Geng 5,  Camille Lobry 1,  Jasper Mullenders 1,  Bryan King 1,  Thomas Trimarchi 1,  Beatriz Aranda-Orgilles 1,  Cynthia Liu 6,  Steven Shen 7,  Amit K Verma 3,  Rudolf Jaenisch 2,  Iannis Aifantis 1
Affiliations

Affiliations

  • 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.
PMID: 25867473 DOI: 10.1038/ni.3148
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.

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