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Text
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URL Address
<a href="http://doi.org/10.1371/journal.pone.0080898" target="_blank" rel="noreferrer noopener">http://doi.org/10.1371/journal.pone.0080898</a>
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Pages
16-16
Issue
11
Volume
8
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Title
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Tumor-specific Chromosome Mis-segregation Controls Cancer Plasticity By Maintaining Tumor Heterogeneity
Publisher
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Plos One
Date
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2013
2013-11
Subject
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aneuploidy; clonal evolution; expression; glioblastoma-multiforme; glioma-cells; growth-factor; initiating cells; malignant glioma; mitotic errors; Science & Technology - Other Topics; stem-cells
Creator
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Hu Y J; Ru N; Xiao H S; Chaturbedi A; Hoa N T; Tian X J; Zhang H; Ke C; Yan F R; Nelson J; Li Z Z; Gramer R; Yu L P; Siegel E; Zhang X N; Jia Z Y; Jadus M R; Limoli C L; Linskey M E; Xing J H; Zhou Y H
Description
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Aneuploidy with chromosome instability is a cancer hallmark. We studied chromosome 7 (Chr7) copy number variation (CNV) in gliomas and in primary cultures derived from them. We found tumor heterogeneity with cells having Chr7-CNV commonly occurs in gliomas, with a higher percentage of cells in high-grade gliomas carrying more than 2 copies of Chr7, as compared to low-grade gliomas. Interestingly, all Chr7-aneuploid cell types in the parental culture of established glioma cell lines reappeared in single-cell-derived subcultures. We then characterized the biology of three syngeneic glioma cultures dominated by different Chr7-aneuploid cell types. We found phenotypic divergence for cells following Chr7 mis-segregation, which benefited overall tumor growth in vitro and in vivo. Mathematical modeling suggested the involvement of chromosome instability and interactions among cell subpopulations in restoring the optimal equilibrium of tumor cell types. Both our experimental data and mathematical modeling demonstrated that the complexity of tumor heterogeneity could be enhanced by the existence of chromosomes with structural abnormality, in addition to their mis-segregations. Overall, our findings show, for the first time, the involvement of chromosome instability in maintaining tumor heterogeneity, which underlies the enhanced growth, persistence and treatment resistance of cancers.
Identifier
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<a href="http://doi.org/10.1371/journal.pone.0080898" target="_blank" rel="noreferrer noopener">10.1371/journal.pone.0080898</a>
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Journal Article or Conference Abstract Publication
2013
aneuploidy
Chaturbedi A
clonal evolution
expression
glioblastoma-multiforme
glioma-cells
Gramer R
growth-factor
Hoa N T
Hu Y J
initiating cells
Jadus M R
Jia Z Y
Journal Article or Conference Abstract Publication
Ke C
Li Z Z
Limoli C L
Linskey M E
malignant glioma
mitotic errors
Nelson J
PloS one
Ru N
Science & Technology - Other Topics
Siegel E
stem-cells
Tian X J
Xiao H S
Xing J H
Yan F R
Yu L P
Zhang H
Zhang X N
Zhou Y H