TET deficiency drives selection of aneuploid cells in mice

In mice, invariant natural killer T cells lacking Tet2 and Tet3 drove aggressive lymphoid expansion consistently marked by recurrent chromosome 17 trisomy. Researchers observed this dominant aneuploid state across more than ten independently derived tumors after transplantation into immunocompetent recipient mice. Single-cell whole-genome sequencing of cultured, proliferating mouse cells revealed that rare cells harboring chromosome 17 trisomy appeared shortly after Tet deletion in the thymus alongside other copy number alterations, but only these trisomic cells progressively enriched during cellular expansion. Inducibly Tet-deficient mouse embryonic stem cells similarly selected for pre-existing aneuploid states, including chromosome 6 trisomy. Reanalysis of datasets from Dnmt3a-deficient mouse lymphomas also identified recurrent chromosome gains, including chromosome 17 trisomy.