title: TET1 is a tumor suppressor of hematopoietic malignancy.
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.
authors: 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.
authors: Luisa
authors: L
authors: Cimmino
authors: 1] Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA. [2] Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors: Meelad M
authors: MM
authors: Dawlaty
authors: 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.
authors: Delphine
authors: D
authors: Ndiaye-Lobry
authors: 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.
authors: Yoon Sing
authors: YS
authors: Yap
authors: 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.
authors: Sofia
authors: S
authors: Bakogianni
authors: Department of Hemato-Oncology, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, New York, USA.
authors: Yiting
authors: Y
authors: Yu
authors: Department of Hemato-Oncology, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, New York, USA.
authors: Sanchari
authors: S
authors: Bhattacharyya
authors: Department of Medicine, Weill Cornell Medical College, Cornell University, New York, New York, USA.
authors: Rita
authors: R
authors: Shaknovich
authors: Department of Laboratory Medicine, University of California San Francisco, San Francisco, California, USA.
authors: Huimin
authors: H
authors: Geng
authors: 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.
authors: Camille
authors: C
authors: Lobry
authors: 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.
authors: Jasper
authors: J
authors: Mullenders
authors: 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.
authors: Bryan
authors: B
authors: King
authors: 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.
authors: Thomas
authors: T
authors: Trimarchi
authors: 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.
authors: Beatriz
authors: B
authors: Aranda-Orgilles
authors: Howard Hughes Medical Institute and Department of Pathology, NYU School of Medicine, New York, New York, USA.
authors: Cynthia
authors: C
authors: Liu
authors: Center for Health Informatics and Bioinformatics, NYU School of Medicine, New York, New York, USA.
authors: Steven
authors: S
authors: Shen
authors: Department of Hemato-Oncology, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, New York, USA.
authors: Amit K
authors: AK
authors: Verma
authors: 1] Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA. [2] Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors: Rudolf
authors: R
authors: Jaenisch
authors: 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.
authors: Iannis
authors: I
authors: Aifantis
mesh_terms: D044503:5-Methylcytosine / Q000031:analogs & derivatives; D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D043171:Chromosomal Instability; D003596:Cytosine / Q000031:analogs & derivatives* / Q000378:metabolism; D019175:DNA Methylation; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000502:physiology*; D044127:Epigenesis, Genetic; D059472:Exome / Q000235:genetics; D020869:Gene Expression Profiling; D006801:Humans; D016393:Lymphoma, B-Cell / Q000235:genetics*; D051379:Mice; D009154:Mutation / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; C540839:TET1 protein, mouse; D025521:Tumor Suppressor Proteins; C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D003596:Cytosine