Clonal selection of stable aneuploidies in progenitor cells drives high-prevalence tumorigenesis.

ABSTRACT: Chromosome gains and losses are a frequent feature of human cancers. However, how these aberrations can outweigh the detrimental effects of aneuploidy remains unclear. An initial comparison of existing chromosomal instability (CIN) mouse models suggests that aneuploidy accumulates to low levels in these animals. We therefore developed a novel mouse model that enables unprecedented levels of chromosome missegregation in the adult animal. At the earliest stages of T-cell development, cells with random chromosome gains and/or losses are selected against, but CIN eventually results in the expansion of progenitors with clonal chromosomal imbalances. Clonal selection leads to the development of T-cell lymphomas with stereotypic karyotypes in which chromosome 15, containing the Myc oncogen

SUBMITTER: Trakala M 

PROVIDER: S-EPMC8336892 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature