Magee Womens Hospital of UPMC, Pittsburgh, PA 15213, USA.
Gynecol Oncol. 2012 Jun;125(3):677-82. doi: 10.1016/j.ygyno.2012.03.006. Epub 2012 Mar 8.
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).
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.
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).
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.
本研究旨在确定一组未经选择的晚期上皮性卵巢癌（EOC）患者中铂敏感和铂耐药肿瘤的 BRCA1/2 缺陷率。
对 29 例铂敏感 EOC 患者和 24 例铂耐药患者进行了 BRCA1/2 突变分析。当有正常组织时，对突变携带者进行了种系 DNA 分析。通过定量 RT-PCR 确定 BRCA 表达。分析了 BRCA 突变状态和表达水平与铂类反应参数之间的关系。
53 例 EOC 肿瘤中有 15 例（28.3%）存在 BRCA1/2 突变。12 个突变发生在 BRCA1 中，而 3 个涉及 BRCA2。在有正常组织可供 DNA 分析的 12 名突变携带者中，33.3%的突变被发现是体细胞突变。有 3 个突变是新的。大多数 BRCA 突变（73%）发生在铂敏感疾病患者中。总的来说，铂敏感肿瘤中有 38%发现 BRCA 突变，而铂耐药患者中只有 17%。BRCA 突变携带者中观察到铂敏感疾病的趋势（p=0.079）。19 名（36%）研究患者存在某种形式的 BRCA 缺陷，这些患者铂耐药肿瘤的可能性较低（OR=0.29；p 值=0.048）。
BRCA 突变在铂敏感 EOC 中比铂耐药疾病更常见。EOC 中 BRCA 缺陷的总体高频率强调了肿瘤分析的重要性，因为正在研究针对 DNA 修复途径的治疗方法。
