Variation in topoisomerase I gene copy number as a mechanism for intrinsic drug sensitivity

Br J Cancer. 1996 Aug;74(4):508-12. doi: 10.1038/bjc.1996.394.


DNA topoisomerase I (topo I) is the principle target for camptothecin and its derivatives such as SN38. Levels of topo I expression vary widely between and within tumour types and the basis for this is poorly understood. We have used fluorescence in situ hybridisation to detect the topo I locus in a panel of breast and colon cancer cell lines. This approach has identified a range of topo I gene copies from 1 to 6 between the cell lines as a result of DNA amplification, polysomy and isochromosome formation. Topo I gene copy number was highly correlated with topo I expression, (rs = 0.92), and inversely correlated to sensitivity to a 1 h exposure to SN38 (rs = -0.904). This illustrates the significant impact of altered topo I gene copy number on intrinsic drug sensitivity and influences potential mechanisms for acquisition of drug resistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / toxicity*
  • Breast Neoplasms
  • Camptothecin / analogs & derivatives*
  • Camptothecin / toxicity
  • Cell Line
  • Cell Survival / drug effects
  • Colonic Neoplasms
  • DNA Topoisomerases, Type I / biosynthesis
  • DNA Topoisomerases, Type I / genetics*
  • Drug Resistance, Neoplasm*
  • Female
  • Gene Amplification
  • Gene Expression
  • Genetic Variation*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Irinotecan
  • Karyotyping
  • Kinetics
  • Nuclear Proteins / metabolism
  • Tumor Cells, Cultured


  • Antineoplastic Agents, Phytogenic
  • Nuclear Proteins
  • Irinotecan
  • DNA Topoisomerases, Type I
  • Camptothecin