Single-chromosome Gains Commonly Function as Tumor Suppressors
Name
nihms908957.pdf
Size
2.84 MB
Format
Adobe PDF
Checksum (MD5)
c3c35624dafd24a7d39cb429060c38cf
Author(s)
Chung, Erica S.
Sayles, Nicole M.
Passerini, Verena
Storchova, Zuzana
Sheltzer, Jason Meyer
Ko, Julie H.
Replogle, John Michael
Habibe Burgos, Nicole C.
Meehl, Colleen M.
Amon, Angelika B.
Date Issued
January 2017
Journal
Cancer Cell
Publisher
Elsevier BV
Citation
Sheltzer, Jason M. et al. “Single-Chromosome Gains Commonly Function as Tumor Suppressors.” Cancer Cell 31, 2 (February 2017): 240–255 © 2017 Elsevier Inc
Version
Author's final manuscript
Abstract
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.Keywords:
aneuploidy; genome dosage imbalance; genomic instability; transformation; chromosomal instability
MIT Department
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
Persistent DSpace Link
DOI of Published Version
http://dx.doi.org/10.1016/J.CCELL.2016.12.004
