Mapping karyotypic heterogeneity in chromosomal instable murine T-cell acute lymphoblastic lymphomas using single-cell sequencing
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ABSTRACT: Chromosome instability (CIN) leads to aneuploidy and copy number variations (CNVs). Even though both are hallmarks of cancer cells, aneuploidy inhibits proliferation of untransformed cells, suggesting that cancer cells have adapted to cope with CIN. The spindle assembly checkpoint (SAC) prevents CIN by monitoring chromosome attachment and sister chromatid tension in mitosis. By conditionally inactivating Mad2, an essential SAC gene, we find that SAC inactivation in T-cells or hepatocytes is remarkably well tolerated and becomes tumorigenic when placed in a p53null or p53+/- predisposed background. The resulting T-ALLs and HCCs are highly aneuploid, exhibit clonal copy number changes that are tumor specific despite ongoing CIN, indicating that CIN is a powerful driver of tumor evolution.
ORGANISM(S): Mus musculus
PROVIDER: GSE63688 | GEO | 2017/03/20
SECONDARY ACCESSION(S): PRJNA268693
REPOSITORIES: GEO
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