TET1 is a tumor suppressor of hematopoietic malignancy. Academic Article uri icon

Overview

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.

publication date

  • April 13, 2015

Research

keywords

  • B-Lymphocytes
  • Cytosine
  • DNA-Binding Proteins
  • Embryonic Stem Cells
  • Lymphoma, B-Cell
  • Proto-Oncogene Proteins
  • Tumor Suppressor Proteins

Identity

PubMed Central ID

  • PMC4545281

Scopus Document Identifier

  • 84929895270

Digital Object Identifier (DOI)

  • 10.1371/journal.pgen.1002781

PubMed ID

  • 25867473

Additional Document Info

volume

  • 16

issue

  • 6