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

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 year

  1996

• Venue

  British Journal of Cancer

• Publication date

  1996-08-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1038/bjc.1996.394PMID 8761363PMCID 2074660
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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