TOP1gene copy numbers in colorectal cancer samples and cell lines and their association toin vitrodrug sensitivity
| Autor: | Nils Brünner, Signe Lykke Nielsen, Kirsten Vang Nielsen, Maria Unni Rømer, Niels Frank Jensen, Hans Jørgen Nielsen, Sven Müller |
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| Rok vydání: | 2011 |
| Předmět: |
Organoplatinum Compounds
Cell Survival Colorectal cancer Gene Dosage Biology Irinotecan Statistics Nonparametric Cell Line Tumor medicine Humans Copy-number variation neoplasms In Situ Hybridization Fluorescence Cell Death Gastroenterology medicine.disease digestive system diseases Epithelium Oxaliplatin medicine.anatomical_structure DNA Topoisomerases Type I Drug Resistance Neoplasm Cell culture Cancer research Biomarker (medicine) Camptothecin Chromosome 20 Colorectal Neoplasms medicine.drug |
| Zdroj: | Scandinavian Journal of Gastroenterology. 47:68-79 |
| ISSN: | 1502-7708 0036-5521 |
| Popis: | A positive relationship between topoisomerase-1 (TOP1) protein and sensitivity toward the TOP1 inhibitor irinotecan has been reported in patients with metastatic colorectal cancer (mCRC). In this study, we analyzed TOP1 gene copy number variation in tumor tissue from CRC patients and CRC cell lines with different sensitivities to the TOP1 inhibitor SN-38 and oxaliplatin.A TOP1 gene probe with a chromosome 20 centromere (CEN-20) reference probe was applied on normal mucosa and on tumor tissue from 50 stage III CRC patients. Additionally, associations between TOP1/CEN-20 ratio and in vitro sensitivity to SN-38 (irinotecan) and oxaliplatin were tested on 10 CRC cell lines. Results. In the malignant epithelium, 84% of the samples demonstrated an increased TOP1 gene copy number and 64% had an increased TOP1/CEN-20 ratio compared with the non-affected mucosa. Sixteen (32%) of the tumors had a ratio of ≥ 1.5 and 9 (18%) of these had a ratio of ≥ 2.0. A positive association was observed between the TOP1 gene copy number and the TOP1/CEN-20 ratio and in vitro sensitivity toward SN-38, but not toward oxaliplatin.A large fraction of the clinical samples demonstrated increased TOP1 gene copy number and increased TOP1/CEN-20 ratio. The cell line study suggested an association between TOP1 gene copy number or TOP1/CEN-20 ratio and sensitivity to irinotecan but not oxaliplatin. |
| Databáze: | OpenAIRE |
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