Condensin II mutation causes T-cell lymphoma through tissue-specific genome instability.

ABSTRACT: Chromosomal instability is a hallmark of cancer, but mitotic regulators are rarely mutated in tumors. Mutations in the condensin complexes, which restructure chromosomes to facilitate segregation during mitosis, are significantly enriched in cancer genomes, but experimental evidence implicating condensin dysfunction in tumorigenesis is lacking. We report that mice inheriting missense mutations in a condensin II subunit (Caph2^nes) develop T-cell lymphoma. Before tumors develop, we found that the same Caph2 mutation impairs ploidy maintenance to a different extent in different hematopoietic cell types, with ploidy most severely perturbed at the CD4⁺CD8⁺ T-cell stage from which tumors initiate. Premalignant CD4⁺CD8⁺ T cells show persisten

SUBMITTER: Woodward J 

PROVIDER: S-EPMC5088566 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature