Extrachromosomal oncogene amplification in tumour pathogenesis and evolution

Nat Rev Cancer. 2019 May;19(5):283-288. doi: 10.1038/s41568-019-0128-6.

Abstract

Recent reports have demonstrated that oncogene amplification on extrachromosomal DNA (ecDNA) is a frequent event in cancer, providing new momentum to explore a phenomenon first discovered several decades ago. The direct consequence of ecDNA gains in these cases is an increase in DNA copy number of the oncogenes residing on the extrachromosomal element. A secondary effect, perhaps even more important, is that the unequal segregation of ecDNA from a parental tumour cell to offspring cells rapidly increases tumour heterogeneity, thus providing the tumour with an additional array of responses to microenvironment-induced and therapy-induced stress factors and perhaps providing an evolutionary advantage. This Perspectives article discusses the current knowledge and potential implications of oncogene amplification on ecDNA in cancer.

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

  • Animals
  • Chromosomes / genetics*
  • DNA Copy Number Variations / genetics
  • Gene Amplification / genetics*
  • Humans
  • Neoplasms / genetics*
  • Neoplasms / pathology*
  • Oncogenes / genetics*
  • Tumor Microenvironment / genetics