BRCA1/2 mutations and expression: Response to platinum chemotherapy in patients with advanced stage epithelial ovarian cancer

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• 作者：Rebecca Byler Dann^a ; Julie A. DeLoia^b ; Kirsten M. Timms^c ; Kristin K. Zorn^a ; Jennifer Potter^c ; Darl D. Flake II^c ; Jerry S. Lanchbury^c ; Thomas C. Krivak^a ; ^{tkrivak@mail.magee.edu}
• 关键词：BRCA mutations ; Ovarian cancer
• 刊名：Gynecologic Oncology
• 出版年：2012
• 期刊代码：295_00908258
• 类别：med
• 出版时间：June, 2012
• 卷：125
• 期：3
• 页码：677-682
• 文件大小：329 K

摘要

Objective

Our objective was to determine the rate of BRCA1/2 deficiency in platinum-sensitive and platinum-resistant tumors from a cohort of unselect patients with advanced epithelial ovarian cancer (EOH).

Methods

BRCA1/2 mutation analysis was performed in 29 patients with platinum-sensitive EOC and 24 patients with platinum-resistant disease. Germline DNA was analyzed in mutation carriers when normal tissue was available. BRCA expression was ascertained by quantitative rt-PCR. Associations between BRCA mutation status and expression levels and parameters of platinum response were analyzed.

Results

Fifteen of 53 (28.3%) EOC tumors had BRCA1/2 mutations. Twelve mutations were in BRCA1, while 3 involved BRCA2. Of the 12 mutation-carriers with normal tissue available for DNA analyses, 33.3%of the mutations were found to be somatic. Three mutations were novel. The majority of BRCA mutations (73%) were identified in patients with platinum-sensitive disease. In total, 38%of platinum-sensitive tumors were found to have a BRCA mutation, compared to 17%of the platinum-resistant patients. A statistical trend toward platinum-sensitive disease was seen in BRCA mutation carriers (p = 0.079). Nineteen (36%) study patients had some form of BRCA deficiency, and these patients were less likely to have platinum-resistant tumors (OR = 0.29; p value = 0.048).

Conclusions

BRCA mutations occurred more frequently in platinum-sensitive EOC than platinum-resistant disease. The high overall frequency of BRCA deficiency in EOC underscores the importance of tumor profiling as therapies targeting the DNA repair pathway are being investigated.