Genomic and Functional Approaches to Understanding Cancer Aneuploidy

Cancer Cell. 2018 Apr 9;33(4):676-689.e3. doi: 10.1016/j.ccell.2018.03.007. Epub 2018 Apr 2.

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.

Keywords: aneuploidy; cancer genomics; genome engineering; lung squamous cell carcinoma.

Publication types

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

MeSH terms

  • Aneuploidy*
  • Carcinoma, Squamous Cell / genetics*
  • Cell Cycle
  • Cell Proliferation
  • Chromosome Aberrations
  • Chromosome Deletion
  • Chromosomes, Human, Pair 3 / genetics
  • Databases, Genetic
  • Genomics / methods*
  • Humans
  • Mutation Rate
  • Tumor Suppressor Protein p53 / genetics*

Substances

  • TP53 protein, human
  • Tumor Suppressor Protein p53