Differential oncogene amplification in tumor cells from a patient treated with cisplatin and 5-fluorouracil

Abstract Peritoneal cells were derived from a patient (PK) with adenocarcinoma of the colon during the course of cisplatin/ 5 -fluorouracil ( 5 -FUra) treatment. Resistance to cisplatin and 5 -FUra, characterized by a lack of response to chemotherapy and continued growth of the tumor, was concomitantly associated with a 2–4 -fold increase in DNA copy number for dTMP synthase and dihydrofolate reductase. There was a corresponding amplification in DNA copy number of the c- myc ( 2× ), H-ras ( 4× ), and c- fos ( 15× ) oncogenes. Cytogenetic studies revealed an iso ( 13 q) chromosome, but failed to show any double minutes or homogeneously staining regions. In addition, drug-resistant tumor cells from PK and another patient (HG) displayed enhanced expression of dTMP synthase, c- fos and DNA polymerase β when compared to normal colon tissue and the HCT 8 human colon carcinoma cell line. These results suggest that elevated oncogene DNA and gene expression may be involved in the development of cisplatin resistance.