Gene amplification: Mechanisms and involvement in cancer

Atsuka Matsui, Tatsuya Ihara, Hiraku Suda, Hirofumi Mikami, Kentaro Semba

Research output: Contribution to journalReview article

33 Citations (Scopus)

Abstract

Gene amplification was recognized as a physiological process during the development of Drosophila melanogaster. Intriguingly, mammalian cells use this mechanism to overexpress particular genes for survival under stress, such as during exposure to cytotoxic drugs. One well-known example is the amplification of the dihydrofolate reductase gene observed in methotrexate- resistant cells. Four models have been proposed for the generation of amplifications: extrareplication and recombination, the breakage-fusion-bridge cycle, double rolling-circle replication, and replication fork stalling and template switching. Gene amplification is a typical genetic alteration in cancer, and historically many oncogenes have been identified in the amplified regions. In this regard, novel cancer-associated genes may remain to be identified in the amplified regions. Recent comprehensive approaches have further revealed that co-amplified genes also contribute to tumorigenesis in concert with known oncogenes in the same amplicons. Considering that cancer develops through the alteration of multiple genes, gene amplification is an effective acceleration machinery to promote tumorigenesis. Identification of cancer-associated genes could provide novel and effective therapeutic targets.

Original languageEnglish
Pages (from-to)567-582
Number of pages16
JournalBiomolecular Concepts
Volume4
Issue number6
DOIs
Publication statusPublished - 2013 Dec 1

Keywords

  • Amplicon
  • Cancer
  • Development
  • Drug resistance
  • Microarray

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Gene amplification: Mechanisms and involvement in cancer'. Together they form a unique fingerprint.

  • Cite this