| First Author | Cimmino L | Year | 2015 |
| Journal | Nat Immunol | Volume | 16 |
| Issue | 6 | Pages | 653-62 |
| PubMed ID | 25867473 | Mgi Jnum | J:232667 |
| Mgi Id | MGI:5779775 | Doi | 10.1038/ni.3148 |
| Citation | Cimmino L, et al. (2015) TET1 is a tumor suppressor of hematopoietic malignancy. Nat Immunol 16(6):653-62 |
| abstractText | 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. |
