The Multifaceted Role of Chromosomal Instability in Cancer and Its Microenvironment

Cell. 2018 Sep 6;174(6):1347-1360. doi: 10.1016/j.cell.2018.08.027.


Chromosomal instability (CIN) is a hallmark of human cancer, and it is associated with poor prognosis, metastasis, and therapeutic resistance. CIN results from errors in chromosome segregation during mitosis, leading to structural and numerical chromosomal abnormalities. In addition to generating genomic heterogeneity that acts as a substrate for natural selection, CIN promotes inflammatory signaling by introducing double-stranded DNA into the cytosol, engaging the cGAS-STING anti-viral pathway. These multipronged effects distinguish CIN as a central driver of tumor evolution and as a genomic source for the crosstalk between the tumor and its microenvironment, in the course of immune editing and evasion.

Publication types

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

MeSH terms

  • Aneuploidy
  • Chromosomal Instability*
  • Humans
  • Immunity, Innate
  • Interferon Type I / metabolism
  • Membrane Proteins / metabolism
  • Neoplasms / immunology
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Nucleotidyltransferases / metabolism
  • Signal Transduction
  • Tumor Microenvironment


  • Interferon Type I
  • Membrane Proteins
  • STING1 protein, human
  • Nucleotidyltransferases