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Cancer Cell. 2017 Feb 13;31(2):240-255. doi: 10.1016/j.ccell.2016.12.004. Epub 2017 Jan 12.

Single-chromosome Gains Commonly Function as Tumor Suppressors.

Author information

1
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; David H. Koch Institute for Integrative Cancer Research, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: sheltzer@cshl.edu.
2
David H. Koch Institute for Integrative Cancer Research, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
3
Albert Einstein College of Medicine, Bronx, NY 10461, USA.
4
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
5
Group Maintenance of Genome Stability, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
6
Group Maintenance of Genome Stability, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany; Department of Molecular Genetics, University of Kaiserslautern, 67663 Kaiserslautern, Germany.
7
David H. Koch Institute for Integrative Cancer Research, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: angelika@mit.edu.

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; chromosomal instability; genome dosage imbalance; genomic instability; transformation

PMID:
28089890
PMCID:
PMC5713901
DOI:
10.1016/j.ccell.2016.12.004
[Indexed for MEDLINE]
Free PMC Article

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