Single-chromosome Gains Commonly Function as Tumor Suppressors

Cancer Cell. 2017 Feb 13;31(2):240-255. doi: 10.1016/j.ccell.2016.12.004. Epub 2017 Jan 12.

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.

Keywords: aneuploidy; chromosomal instability; genome dosage imbalance; genomic instability; transformation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aneuploidy*
  • Animals
  • Cell Proliferation
  • Cell Transformation, Neoplastic
  • Chromosome Aberrations*
  • Genes, ras
  • Genomic Instability
  • HCT116 Cells
  • Humans
  • Neoplasms / genetics*
  • Neoplasms / prevention & control
  • Oncogenes