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Concomitant loss of TET2 and TET3 results in T cell expansion and genomic instability

ABSTRACT: TET proteins are tumor suppressors that through their catalytic activity oxidize 5-methylcytosine to 5-hydroxymethylcytosine, to promote DNA demethylation and to regulate gene expression. Notably, TET2 is the second most frequently mutated gene in hematological malignancies, including T cell lymphomas. However, murine models with deletion of TET2 do not exhibit T cell expansion, presumably due to redundancy with other members of the TET family of proteins. In order to gain insight on the TET mediated molecular events that safeguard T cells from aberrant proliferation we performed serial adoptive transfers of murine CD4 T cells that lack concomitantly TET2 and TET3 to fully immunocompetent congenic mice. Our data reveal a progressive acquisition of malignant traits upon loss of TET2 and TET3 that is characterized by loss of genomic integrity, acquisition of aneuploidy and upregulation of the protooncogene Myc.

ORGANISM(S): Mus musculus

PROVIDER: GSE278239 | GEO | 2024/11/11

REPOSITORIES: GEO

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Concomitant loss of TET2 and TET3 results in T cell expansion and genomic instability [WGS]

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