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[Comparative genomic hybridization for analysis of chromosomal changes in cisplatin-resistant ovarian cancer]
K Kudoh1, M Takano, T Koshikawa
1Department of Obstetrics and Gynecology, Self Defense Force Sendai Hospital, 1-1 Minaminometate, Miyagino-ku, Sendai, Miyagi 983-8580, Japan. k2-kudoh@xa2.so-net.ne.jp
Abstract:
In our attempt to find characteristic genetic changes in resistant tumors, we screened the whole genome for gene aberrations in 28 primary ovarian cancers, using the comparative genomic hybridization (CGH) method. These cancers included 14 tumors from patients who did not respond to cisplatin-based combination chemotherapy in comparison with 14 tumors from patients who completely responded to the chemotherapy. We found gains in chromosomal region 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 found to be 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 for cisplatin-based chemotherapy in ovarian cancer patients based on the CGH analysis. Present findings suggest that these chromosomal gains may be potential indicators for prediction of resistance in ovarian cancer patients prior to cisplatin-based chemotherapy.
Insights
Genomic aberrations, specifically gains in chromosomal regions 1q21-q22 and 13q12-q14, are linked to cisplatin resistance in ovarian cancer. These findings may help predict patient response to chemotherapy.
Area of Science:
- Genomics
- Oncology
- Cancer Genetics
Context:
- Ovarian cancer treatment often involves cisplatin-based chemotherapy.
- Drug resistance significantly impacts patient outcomes.
- Identifying genetic markers for resistance is crucial for personalized medicine.
Purpose:
- To identify characteristic genetic changes associated with cisplatin resistance in primary ovarian cancers.
- To compare whole-genome gene aberrations between drug-sensitive and drug-resistant tumors.
Summary:
- Comparative genomic hybridization (CGH) was used to screen 28 primary ovarian cancers (14 resistant, 14 sensitive to cisplatin).
- Gains in chromosomal regions 1q21-q22 and 13q12-q14 were significantly associated with the drug-resistant phenotype.
- These regions harbor genes involved in transcription, oncogenesis, cell cycle regulation, and apoptosis, suggesting their role in modulating cellular response to chemotherapy.
Impact:
- This study provides the first CGH-based evidence linking specific genomic aberrations to clinical resistance to cisplatin chemotherapy in ovarian cancer.
- The identified chromosomal gains may serve as potential predictive biomarkers for assessing patient resistance prior to treatment.
- Findings pave the way for developing targeted strategies to overcome chemotherapy resistance.