COMPARATIVE GENOMIC HYBRIDIZATION ANALYSIS OF CHROMOSOMAL ALTERATIONSINDUCED BY THE DEVELOPMENT OF RESISTANCE TO THYMIDYLATE SYNTHASE INHIBITORS

Acquired resistance to chemotherapy is a major obstacle to the success ful treatment of cancer. In the past, technical limitations prevented the detection of genetic alterations associated with such resistance o n a genome-wide scale. This study evaluated comparative genomic hybrid ization (CGH) as a tool to detect candidate regions of the genome asso ciated with chemoresistance. Using a variation of conventional CGH, DN A from cell lines that were resistant to thymidylate synthase inhibito rs (raltitrexed and 5-fluorouracil) and their sensitive parent cells w ere evaluated. In MCF-7 and H630 cells that were resistant to raltitre xed, only a single region of change (18p gain) was apparent. The third cell line, H630R10, which was resistant to 5-fluorouracil, had change s in several genomic regions following the acquisition of resistance, including 18p gain. Gain in the chromosomal region containing the thym idylate synthase gene (18p11.32) was detected by CGH in all three resi stant cell lines. However, additional novel regions of interest mere i dentified in the cells that were resistant to 5-fluorouracil, These re sults suggest that CGH is of potential use in the detection of regions of the genome involved in chemoresistance.