TET1 is a tumor suppressor of hematopoietic malignancy

Luisa Cimmino, Meelad M. Dawlaty, Delphine Ndiaye-Lobry, Yoon Sing Yap, Sofia Bakogianni, Yiting Yu, Sanchari Bhattacharyya, Rita Shaknovich, Huimin Geng, Camille Lobry, Jasper Mullenders, Bryan King, Thomas Trimarchi, Beatriz Aranda-Orgilles, Cynthia Liu, Steven Shen, Amit K. Verma, Rudolf Jaenisch, Iannis Aifantis

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)653-662
Number of pages10
JournalNature Immunology
Volume16
Issue number6
DOIs
StatePublished - May 19 2015

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Hematologic Neoplasms
Maintenance
B-Cell Lymphoma
Exome
Dioxygenases
Neoplasms
Normal Distribution
Cell Lineage
Embryonic Stem Cells
Epigenomics
DNA Repair
Non-Hodgkin's Lymphoma
B-Lymphocytes
Chromosomes
Mutation
DNA
Genes
5-hydroxymethylcytosine
Proteins

ASJC Scopus subject areas

  • Immunology

Cite this

Cimmino, L., Dawlaty, M. M., Ndiaye-Lobry, D., Yap, Y. S., Bakogianni, S., Yu, Y., ... Aifantis, I. (2015). TET1 is a tumor suppressor of hematopoietic malignancy. Nature Immunology, 16(6), 653-662. https://doi.org/10.1038/ni.3148

TET1 is a tumor suppressor of hematopoietic malignancy. / Cimmino, Luisa; Dawlaty, Meelad M.; Ndiaye-Lobry, Delphine; Yap, Yoon Sing; Bakogianni, Sofia; Yu, Yiting; Bhattacharyya, Sanchari; Shaknovich, Rita; Geng, Huimin; Lobry, Camille; Mullenders, Jasper; King, Bryan; Trimarchi, Thomas; Aranda-Orgilles, Beatriz; Liu, Cynthia; Shen, Steven; Verma, Amit K.; Jaenisch, Rudolf; Aifantis, Iannis.

In: Nature Immunology, Vol. 16, No. 6, 19.05.2015, p. 653-662.

Research output: Contribution to journalArticle

Cimmino, L, Dawlaty, MM, Ndiaye-Lobry, D, Yap, YS, Bakogianni, S, Yu, Y, Bhattacharyya, S, Shaknovich, R, Geng, H, Lobry, C, Mullenders, J, King, B, Trimarchi, T, Aranda-Orgilles, B, Liu, C, Shen, S, Verma, AK, Jaenisch, R & Aifantis, I 2015, 'TET1 is a tumor suppressor of hematopoietic malignancy', Nature Immunology, vol. 16, no. 6, pp. 653-662. https://doi.org/10.1038/ni.3148
Cimmino L, Dawlaty MM, Ndiaye-Lobry D, Yap YS, Bakogianni S, Yu Y et al. TET1 is a tumor suppressor of hematopoietic malignancy. Nature Immunology. 2015 May 19;16(6):653-662. https://doi.org/10.1038/ni.3148
Cimmino, Luisa ; Dawlaty, Meelad M. ; Ndiaye-Lobry, Delphine ; Yap, Yoon Sing ; Bakogianni, Sofia ; Yu, Yiting ; Bhattacharyya, Sanchari ; Shaknovich, Rita ; Geng, Huimin ; Lobry, Camille ; Mullenders, Jasper ; King, Bryan ; Trimarchi, Thomas ; Aranda-Orgilles, Beatriz ; Liu, Cynthia ; Shen, Steven ; Verma, Amit K. ; Jaenisch, Rudolf ; Aifantis, Iannis. / TET1 is a tumor suppressor of hematopoietic malignancy. In: Nature Immunology. 2015 ; Vol. 16, No. 6. pp. 653-662.
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