K. Kudoh et al., Gains of 1q21-q22 and 13q12-q14 are potential indicators for resistance tocisplatin-based chemotherapy in ovarian cancer patients, CLIN CANC R, 5(9), 1999, pp. 2526-2531
The mechanism of drug resistance in ovarian cancer is multifactorial, and a
ccumulation of multiple genetic changes may lead to the drug-resistant phen
otype. In our attempt to find characteristic genetic changes in drug-resist
ant 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-b
ased combination chemotherapy and 14 tumors from patients who had complete
response to the chemotherapy. We found gains in chromosomal regions 1q21-q2
2 and 13q12-q14 to be related to the drug-resistant phenotype in ovarian ca
ncer patients. Several genes encoding transcription factors, oncogenes, cel
l 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 compa
rative 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.