Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania "Luigi Vanvitelli", Via L. Armanni 5, Naples 80138, Italy.
Medical Oncology Unit, SM delle Grazie Hospital, Via Domitiana, Pozzuoli 80078, Italy.
Pathol Res Pract. 2023 Mar;243:154336. doi: 10.1016/j.prp.2023.154336. Epub 2023 Jan 23.
BRCA1 and BRCA2 are onco-suppressor genes involved in the DNA repair mechanism. The presence of BRCA1/2 mutations confers a higher risk of developing several cancer types. To date, the FDA approved various PARP inhibitors to treat selected BRCA1/2 mutated oncologic patients. At first, PARP inhibitors were approved for patients with ovarian and breast cancers, and subsequently for metastatic pancreatic adenocarcinoma and metastatic castration-resistant prostate cancer after the treatment with chemotherapy. The current guidelines for BRCA testing are very heterogeneous between the different types of tumors regarding the diagnostic algorithm and the type of sample to analyze, such as the blood for the germline mutations and the tumoral tissue for the somatic mutations. Few data have currently been described regarding the detection of BRCA1/2 somatic mutations in formalin-fixed paraffin-embedded (FFPE) samples. In this review, we propose an overview of the BRCA mutations in FFPE samples of several cancers, including breast, ovarian, fallopian tube, primary peritoneal, prostate, and pancreatic cancer. We summarize the types and the frequency of BRCA mutations, the guidelines approved for the test, the molecular assays used for the detection and the PARP inhibitors approved for each tumor type.
BRCA1 和 BRCA2 是参与 DNA 修复机制的抑癌基因。BRCA1/2 突变的存在增加了多种癌症类型的发病风险。迄今为止,FDA 已批准多种 PARP 抑制剂用于治疗特定的 BRCA1/2 突变型肿瘤患者。最初,PARP 抑制剂获批用于卵巢癌和乳腺癌患者,随后在化疗后又获批用于转移性胰腺腺癌和转移性去势抵抗性前列腺癌。目前,不同类型肿瘤的 BRCA 检测指南在诊断算法和要分析的样本类型方面存在很大差异,例如用于种系突变的血液和用于体细胞突变的肿瘤组织。目前关于福尔马林固定石蜡包埋(FFPE)样本中 BRCA1/2 体细胞突变检测的描述数据很少。在这篇综述中,我们对包括乳腺癌、卵巢癌、输卵管癌、原发性腹膜癌、前列腺癌和胰腺癌在内的几种癌症的 FFPE 样本中的 BRCA 突变进行了概述。我们总结了 BRCA 突变的类型和频率、获批的检测指南、用于检测的分子检测方法以及每种肿瘤类型获批的 PARP 抑制剂。