Tumor-Specific Chromosome Mis-Segregation Controls Cancer Plasticity by Maintaining Tumor Heterogeneity

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dc.contributor.authorHu, Yuanjieen
dc.contributor.authorRu, Ningen
dc.contributor.authorXiao, Huashengen
dc.contributor.authorChaturbedi, Abhisheken
dc.contributor.authorHoa, Neil T.en
dc.contributor.authorTian, Xiao-Junen
dc.contributor.authorZhang, Hangen
dc.contributor.authorKe, Chaoen
dc.contributor.authorYan, Fengrongen
dc.contributor.authorNelson, Jodien
dc.contributor.authorLi, Zhenzhien
dc.contributor.authorGramer, Roberten
dc.contributor.authorYu, Lipingen
dc.contributor.authorSiegel, Ericen
dc.contributor.authorZhang, Xiaonaen
dc.contributor.authorJia, Zhenyuen
dc.contributor.authorJadus, Martin R.en
dc.contributor.authorLimoli, Charles L.en
dc.contributor.authorLinskey, Mark E.en
dc.contributor.authorXing, Jianhuaen
dc.contributor.authorZhou, Yi-Hongen
dc.contributor.departmentBiological Sciencesen
dc.date.accessioned2018-10-16T16:41:24Zen
dc.date.available2018-10-16T16:41:24Zen
dc.date.issued2013-09-25en
dc.description.abstractAneuploidy 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.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0080898en
dc.identifier.eissn1932-6203en
dc.identifier.issue11en
dc.identifier.othere80898en
dc.identifier.pmid24282558en
dc.identifier.urihttp://hdl.handle.net/10919/85381en
dc.identifier.volume8en
dc.language.isoenen
dc.publisherPLOSen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleTumor-Specific Chromosome Mis-Segregation Controls Cancer Plasticity by Maintaining Tumor Heterogeneityen
dc.title.serialPLOS ONEen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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