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

GSE278239 Mus musculus Expression profiling by high throughput sequencing 6 samples Submitted 2024/11/11 Platform GPL24247
Summary
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.
Published in
Concomitant loss of TET2 and TET3 results in T cell expansion and genomic instability in mice
Gioulbasani M, Äijö T, Liu S et al. · Communications biology 2024 · PMID 39627458 · doi:10.1038/s42003-024-07312-0
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Also filed as BioProject PRJNA1166157 and SRA study SRP535408. Searching any of these in the dataset finder brings you back here.

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