Single-chromosome Gains Commonly Function as Tumor Suppressors

Publication date: Available online 12 January 2017
Source:Cancer Cell
Author(s): Jason M. Sheltzer, Julie H. Ko, John M. Replogle, Nicole C. Habibe Burgos, Erica S. Chung, Colleen M. Meehl, Nicole M. Sayles, Verena Passerini, Zuzana Storchova, Angelika Amon
Aneuploidy is a hallmark of cancer, although its effects on tumorigenesis are unclear. Here, we investigated the relationship between aneuploidy and cancer development using cells engineered to harbor single extra chromosomes. We found that nearly all trisomic cell lines grew poorly in vitro and as xenografts, relative to genetically matched euploid cells. Moreover, the activation of several oncogenic pathways failed to alleviate the fitness defect induced by aneuploidy. However, following prolonged growth, trisomic cells acquired additional chromosomal alterations that were largely absent from their euploid counterparts and that correlated with improved fitness. Thus, while single-chromosome gains can suppress transformation, the genome-destabilizing effects of aneuploidy confer an evolutionary flexibility that may contribute to the aggressive growth of advanced malignancies with complex karyotypes.

Teaser

By analyzing genetically matched euploid and trisomic cells, Sheltzer et al. find that single-chromosome gains commonly suppress tumorigenicity, and the tumor-suppressive effects of aneuploidy cannot be fully overcome by introducing oncogenic mutations. Following prolonged growth, trisomic cells acquire additional karyotype changes with improved fitness.


http://ift.tt/2imFkiU