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Single-chromosome Gains Commonly Function as Tumor Suppressors.

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.

journal_name

Cancer Cell

journal_title

Cancer cell

authors

Sheltzer JM,Ko JH,Replogle JM,Habibe Burgos NC,Chung ES,Meehl CM,Sayles NM,Passerini V,Storchova Z,Amon A

doi

10.1016/j.ccell.2016.12.004

subject

Has Abstract

pub_date

2017-02-13 00:00:00

pages

240-255

issue

2

eissn

1535-6108

issn

1878-3686

pii

S1535-6108(16)30599-2

journal_volume

31

pub_type

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