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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.

SUBMITTER: Sheltzer JM

PROVIDER: S-EPMC5713901 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Single-chromosome Gains Commonly Function as Tumor Suppressors.

Sheltzer Jason M JM Ko Julie H JH Replogle John M JM Habibe Burgos Nicole C NC Chung Erica S ES Meehl Colleen M CM Sayles Nicole M NM Passerini Verena V Storchova Zuzana Z Amon Angelika A

Cancer cell 20170112 2

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 prolo ...[more]

PMID: 28089890

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