Specific copy number alterations associated with docetaxel/carboplatin response in ovarian carcinomas.
BACKGROUND
The continued high recurrence and mortality rate in ovarian cancer is a significant problem and the major obstacle in the treatment of ovarian cancer patients is chemotherapy resistance. Thus, finding predictive markers of chemoresistance and elucidating resistance mechanisms is crucial for individualising treatment and improving survival of ovarian cancer patients.


METHODS
Using array comparative genomic hybridisation (CGH), this pilot study analysed the tumour genomes of patients treated with docetaxel/carboplatin as first-line chemotherapy (6 resistant versus 24 sensitive cases). This is the first array CGH study of such material.


RESULTS
The study identified genetic alterations specific to chemoresistant (gains in 9p13.2-13.1, 9q21.2-21.32, 9q21.33, 9q22.2-22.31, 9q22.32-22.33 and 9q33.1-34.11) and chemosensitive (losses in 8p23.3-23.1 and 8p22) disease. Additionally, when comparing the results to previously analysed tumour material from patients treated with paclitaxel/carboplatin, the two datasets identified different genetic alteration profiles.


CONCLUSIONS
Specific genetic alterations were identified and associated with chemotherapy response in ovarian cancer. It will be interesting to investigate these exciting data further in larger independent series of ovarian tumours, and hopefully will contribute to the establishment of predictive markers.
Department of Oncology, Institute of Clinical Sciences, University of Gothenburg, SE-413 45 Göteborg, Sweden. lovisa.osterberg@gu.se
Lovisa
L
Osterberg
Kristina
K
Levan
Karolina
K
Partheen
Ulla
U
Delle
Björn
B
Olsson
Karin
K
Sundfeldt
György
G
Horvath
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics*; D016190:Carboplatin / Q000008:administration & dosage; D002874:Chromosome Mapping; D055028:Comparative Genomic Hybridization; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D004273:DNA, Neoplasm / Q000235:genetics; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D018628:Gene Dosage; D020869:Gene Expression Profiling; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D010865:Pilot Projects; D016133:Polymerase Chain Reaction; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D043823:Taxoids; D000077143:Docetaxel; D016190:Carboplatin