A BRCA1/2 Mutational Signature and Survival in Ovarian High-Grade Serous Carcinoma
A BRCA1/2 Mutational Signature and Survival in Ovarian High-Grade Serous Carcinoma
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DOI：
10.1158/1055-9965.epi-16-0286
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发表时间：
2016-11-01
影响因子：
3.8
通讯作者：
Beck, Andrew H.
中科院分区：
文献类型：
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作者：
Dong, Fei;Davineni, Phani K.;Beck, Andrew H.
背景：突变特征已通过癌症基因组的广泛测序确定，并反映了突变发生的潜在过程。突变特征的临床应用尚未明确定义。在此，我们旨在评估突变特征在卵巢高级别浆液性癌中的预后效用。方法：使用来自癌症基因组图谱 (TCGA) 的 310 种卵巢高级别浆液性癌的 15,439 种体细胞突变的开放获取数据来构建贝叶斯模型，以将每种癌症分类为具有或缺乏 BRCA1/2 突变特征。我们在 TCGA 数据集和澳大利亚卵巢癌研究 (AOCS) 的 92 例卵巢高级浆液性癌的独立队列中评估了 BRCA1/2 特征与总生存率的关联。结果：来自 TCGA 且具有 BRCA1/2 突变特征的肿瘤的患者的生存期有所改善（55.2 个月 vs. 38.0 个月），这与 BRCA1/2 基因突变状态、年龄、分期和分级无关（HR = 0.64；P = 0.02）。在 AOCS 数据集中，BRCA1/2 突变特征还与改善的总生存期（46.3 个月与 23.6 个月）相关，与年龄和分期无关（HR = 0.52；P = 0.007）。结论：BRCA1/2 突变特征是卵巢高级别浆液性癌的预后标志物。除了测试 BRCA1/2 突变之外，卵巢癌基因组的突变特征分析可能也很有用。影响：这项研究确定了使用突变特征作为卵巢高级别浆液性癌生存结果的生物标志物。 (C) 2016 年 AACR。
Background: Mutational signatures have been identified by the broad sequencing of cancer genomes and reflect underlying processes of mutagenesis. The clinical application of mutational signatures is not well defined. Here weaim to assess the prognostic utility of mutational signatures in ovarian high-grade serous carcinoma.Methods: Open access data of 15,439 somatic mutations of 310 ovarian high-grade serous carcinomas from The Cancer Genome Atlas (TCGA) are used to construct a Bayesian model to classify each cancer as either having or lacking a BRCA1/2 mutational signature. We evaluate the association of the BRCA1/2 signature with overall survival on the TCGA dataset and on an independent cohort of 92 ovarian high-grade serous carcinomas from the Australian Ovarian Cancer Study (AOCS).Results: Patients from TCGA with tumors harboring the BRCA1/2 mutational signature have improved survival (55.2 months vs. 38.0 months), which is independent of BRCA1/2 gene mutation status, age, stage, and grade (HR = 0.64; P = 0.02). In the AOCS dataset, the BRCA1/2 mutational signature is also associated with improved overall survival (46.3 months vs. 23.6 months) independent of age and stage (HR = 0.52; P = 0.007).Conclusions: A BRCA1/2 mutational signature is a prognostic marker in ovarian high-grade serous carcinoma. Mutational signature analysis of ovarian cancer genomes may be useful in addition to testing for BRCA1/2 mutations.Impact: This study identifies the use of mutational signatures as a biomarker for survival outcome in ovarian high-grade serous carcinoma. (C) 2016 AACR.