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Transient genomic instability drives tumorigenesis through accelerated clonal evolution

ABSTRACT: Abnormal numerical and structural chromosome content is frequently found in human cancer. However, the role of aneuploidy in tumor initiation and progression is poorly understood. To test the effect of aneuploidy on cancer development, we transiently induced chromosome instability (CIN) in mice by inducible overexpression of polo-like kinase 4 (PLK4), a master regulator of centrosome number. Short term increased PLK4 expression generated significant centrosome amplification and aneuploidy resulting in the formation of aggressive T cell lymphomas in mice with heterozygous inactivation of one p53 allele or accelerated tumor development in the absence of p53. Transient CIN increased the frequency of lymphoma-initiating cells, as revealed by T cell receptor sequencing of tumor samples. Transient CIN produced a unique tumor karyotype containing triploid chromosomes 4, 5, 14, and 15, as determined by whole genome sequencing.

ORGANISM(S): Mus musculus

PROVIDER: GSE161728 | GEO | 2021/06/14

REPOSITORIES: GEO

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