Gains of 1q21-q22 and 13q12-q14 are potential indicators for resistance to cisplatin-based chemotherapy in ovarian cancer patients.
The mechanism of drug resistance in ovarian cancer is multifactorial, and accumulation of multiple genetic changes may lead to the drug-resistant phenotype. In our attempt to find characteristic genetic changes in drug-resistant tumors, we screened the whole genome for gene aberrations in 28 primary ovarian cancers using the comparative genomic hybridization method. These cancers included 14 tumors from patients who did not respond to cisplatin-based combination chemotherapy and 14 tumors from patients who had complete response to the chemotherapy. We found gains in chromosomal regions 1q21-q22 and 13q12-q14 to be related to the drug-resistant phenotype in ovarian cancer patients. Several genes encoding transcription factors, oncogenes, cell cycle regulators, and regulators of the apoptotic pathway are located on these regions of the chromosomes, and these genes are potential modulators for toxic insults in cancer cells. This is the first report that shows the relationship between certain genomic aberrations and clinical resistance to cisplatin-based chemotherapy in ovarian cancer patients based on the comparative genomic hybridization analysis. Present findings suggest that these chromosomal gains may be potential indicators for prediction of resistance in ovarian cancer patients before cisplatin-based chemotherapy.
Kudoh
K
K
Department of Obstetrics and Gynecology, National Defense Medical College, Tokorozawa, Saitama, Japan. k2-kudoh@ndmc.ac.jp
Takano
M
M
Koshikawa
T
T
Hirai
M
M
Yoshida
S
S
Mano
Y
Y
Yamamoto
K
K
Ishii
K
K
Kita
T
T
Kikuchi
Y
Y
Nagata
I
I
Miwa
M
M
Uchida
K
K
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D002869:Chromosome Aberrations; D002878:Chromosomes, Human, Pair 1; D002882:Chromosomes, Human, Pair 13; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D009693:Nucleic Acid Hybridization; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D010641:Phenotype
D000970:Antineoplastic Agents; D002945:Cisplatin