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. 1996 Aug;74(4):508–512. doi: 10.1038/bjc.1996.394

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

H L McLeod 1, W N Keith 1
PMCID: PMC2074660  PMID: 8761363

Abstract

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.

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Selected References

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