TET enzyme deficiency drives the selection of specific aneuploid cells in mice
Loss of DNA methylation regulators accelerates clonal expansion by enriching rare pre-existing chromosomal gains such as chromosome 17 trisomy.
bioRxiv · López-Moyado IF et al. · Paper published 1 Oct 2026
In a preprint studying mice, researchers examined how loss of Tet dioxygenases alters genome evolution during cell proliferation. Deleting Tet2 and Tet3 in mouse invariant natural killer T cells drove aggressive lymphoid growth. Across more than ten independent tumors transplanted into immunocompetent mice, the expanded cells consistently carried chromosome 17 trisomy. Single-cell whole-genome sequencing revealed that rare cells with this trisomy appeared shortly after Tet deletion in the thymus. Antigen and interleukin-2 stimulation in culture then progressively enriched these specific aneuploid subclones over other variants. Similarly, inducible Tet deficiency in mouse embryonic stem cells favored pre-existing aneuploidies, including chromosome 6 trisomy. Reanalyzing data from Dnmt3a-deficient mouse lymphomas also uncovered recurrent chromosome gains, demonstrating that disrupting DNA methylation pathways fosters chromosomal instability and selects for proliferative karyotypes.
Why it matters
TET mutations frequently appear in age-related clonal hematopoiesis, and these findings explain how epigenetic alterations can fuel abnormal clonal expansion through chromosomal selection.
Caveats
The findings are based entirely on mouse cells and animal models, and the paper is a preprint that has not yet completed peer review.
Written from the paper’s abstract, and every claim checked against it before publishing. Read the paper for the full methods and data.
The paper
TET loss of function selects for aneuploidies that confer a proliferative advantage
López-Moyado IF, Suzuki K, Hernández-Espinosa L et al.
bioRxiv · 1 Oct 2026 · Preprint, not yet peer-reviewed
- Relevance
- Relevant
- News value
- Notable
- Evidence
- Animals
- Status
- Preprint
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