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


MeSH Major

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


  • 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

  • January 2015



  • Academic Article



  • eng

PubMed Central ID

  • PMC4545281

Digital Object Identifier (DOI)

  • 10.1038/ni.3148

PubMed ID

  • 25867473

Additional Document Info

start page

  • 653

end page

  • 62


  • 16


  • 6