Abstract

Aneuploidy, whole chromosome or chromosome arm imbalance, is a near-universal characteristic of human cancers. In 10,522 cancer genomes from The Cancer Genome Atlas, aneuploidy was correlated with TP53 mutation, somatic mutation rate, and expression of proliferation genes. Aneuploidy was anti-correlated with expression of immune signaling genes, due to decreased leukocyte infiltrates in high-aneuploidy samples. Chromosome arm-level alterations show cancer-specific patterns, including loss of chromosome arm 3p in squamous cancers. We applied genome engineering to delete 3p in lung cells, causing decreased proliferation rescued in part by chromosome 3 duplication. This study defines genomic and phenotypic correlates of cancer aneuploidy and provides an experimental approach to study chromosome arm aneuploidy. Analyzing >10,000 human cancers, Taylor et al. show that aneuploidy is correlated with somatic mutation rate, expression of proliferation genes, and decreased leukocyte infiltration. Loss of chromosome arm 3p is common in squamous cancers, but deletion of chromosome 3p reduces cell proliferation in vitro.

Original languageEnglish (US)
Pages (from-to)676-689.e3
JournalCancer Cell
Volume33
Issue number4
DOIs
StatePublished - Apr 9 2018

Fingerprint

Aneuploidy
Chromosomes
Neoplasms
Genome
Mutation Rate
Leukocytes
Chromosome Duplication
Gene Expression
Chromosomes, Human, Pair 3
Atlases
Cell Proliferation
Lung
Mutation
Genes

Keywords

  • aneuploidy
  • cancer genomics
  • genome engineering
  • lung squamous cell carcinoma

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

Cite this

Genomic and Functional Approaches to Understanding Cancer Aneuploidy. / The Cancer Genome Atlas Research Network.

In: Cancer Cell, Vol. 33, No. 4, 09.04.2018, p. 676-689.e3.

Research output: Contribution to journalArticle

The Cancer Genome Atlas Research Network 2018, 'Genomic and Functional Approaches to Understanding Cancer Aneuploidy', Cancer Cell, vol. 33, no. 4, pp. 676-689.e3. https://doi.org/10.1016/j.ccell.2018.03.007
The Cancer Genome Atlas Research Network. / Genomic and Functional Approaches to Understanding Cancer Aneuploidy. In: Cancer Cell. 2018 ; Vol. 33, No. 4. pp. 676-689.e3.
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