Analyses by comparative genomic hybridization of genes relating with cisplatin-resistance in ovarian cancer.
Cisplatin has played a key-role in the management of ovarian cancer patients. Since the mechanisms of cisplatin-resistance have been reported to be multifactorial, it is quite difficult to predict effectiveness of cisplatin-based chemotherapy. In the present study, we have screened abnormal chromosomal regions in cisplatin-resistant and paclitaxel-resistant human ovarian cancer cell lines using comparative genomic hybridization (CGH). Increased copy number at 6q21-25 and decreased copy number at 7q21-36 and 10q12-15 were observed in the cisplatin-resistant cell line. Increased copy number at 7q11.2-21 was observed in paclitaxel-resistant cell lines. Messenger RNA of MDR1 located on chromosomal region of 7q11.2-21 was overexpressed in the paclitaxel-resistant cell lines and recognized as a potential mechanism of acquired paclitaxel-resistance. In CGH analyses of 28 primary epithelial ovarian cancer patients, gains of 1q21-22 (p = 0.0183) and 13q12-14 (p = 0.0407) were observed in significantly high abundance in the cisplatin-resistant tumor group, compared with the cisplatin-sensitive tumor group. These genetic alterations were suggested to be potential indicators for drug resistance.
Takano
M
M
Kudo
K
K
Goto
T
T
Yamamoto
K
K
Kita
T
T
Kikuchi
Y
Y
D002869:Chromosome Aberrations; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D006801:Humans; D009693:Nucleic Acid Hybridization / Q000379:methods*; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology*; D017239:Paclitaxel / Q000494:pharmacology; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D012334:RNA, Neoplasm; D017239:Paclitaxel; D002945:Cisplatin