Single-chromosome Gains Commonly Function as Tumor Suppressors

Sheltzer, Jason M., Ko, Julie H., Replogle, John M., Habibe Burgos, Nicole C., Chung, Erica S., Meehl, Colleen M., Sayles, Nicole M., Passerini, Verena, Storchova, Zuzana, Amon, Angelika (2017) Single-chromosome Gains Commonly Function as Tumor Suppressors. Cancer Cell, 31 (2). pp. 240-255. ISSN 1535-6108

URL: https://www.ncbi.nlm.nih.gov/pubmed/28089890
DOI: 10.1016/j.ccell.2016.12.004

Abstract

Summary 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.

Item Type: Paper
Uncontrolled Keywords: aneuploidy genome dosage imbalance genomic instability transformation chromosomal instability
Subjects: bioinformatics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > chromosome
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > chromosomes, structure and function > chromosome

bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > tumor suppressor
CSHL Authors:
Communities: CSHL labs > Sheltzer lab
Depositing User: Matt Covey
Date Deposited: 17 Jan 2017 20:26
Last Modified: 07 Sep 2017 18:16
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Dataset ID:
URI: http://repository.cshl.edu/id/eprint/34027

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