Ovarian cancer is the leading cause of mortality among all gynecological cancers in developed countries and its most common and most lethal type is the high-grade serous ovarian carcinoma (HGSC). At the molecular level, nearly half of all HGSCs exhibit ineffective homologous DNA recombination and disruption of DNA damage/repair pathway inactivation caused often by BRCA1 and BRCA2 gene mutation. Recently, the detection of BRCA1/2 mutations became important for personalized treatment of HGSC patients with the PARP-inhibitors in the defined clinical setting of relapse after positive adjuvant platinum-based chemotherapeutic response. Based on the selection of patients by regional oncologists, we attempted to verify the possibilities of BRCA1/2 mutation testing on archival formalin-fixed paraffin-embedded (FFPE) biopsy material from regional hospitals. In the study we used: a/ FFPE tumor resections of 97 patients sent to our laboratory, originally stored in archives of regional departments for a period of 1 - 3 years and retrieved on the principle to contain a maximum of non-necrotic tumor tissue, b/ next-generation sequencing (NGS) assay covering all known mutations in the BRCA1/2 genes on MiSeq (Illumina® platform), and c/ Sophia DDM® bioinformatics platform. After processing of FFPE samples, 5 cases were excluded due to the insufficient genomic DNA quantity. Bioinformatics results of NGS analyses of 92 patients' samples indicated 17.39 % pathogenic mutations and 32.61 % potentially pathogenic mutations in genes BRCA1/2. Overall, 50 % pathogenic and potentially pathogenic mutations were detected in the patient's cohort. The relatively high incidence of BRCA1/2 mutations in our series may be influenced by various indicators including the selection of patients based on adjuvant therapy response as well as regional or population heterogeneity in their frequency. Based on the interdisciplinary cooperation, the use of archival biopsy material processed primarily and stored for longer period in different laboratories without uniformly defined pre-analytical conditions allows identifying the HGSC patients who might better respond to the PARP-inhibition therapy.

中文翻译：

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高级别浆液性卵巢癌和从斯洛伐克患者活检材料中检测失活的 BRCA 基因。

卵巢癌是发达国家所有妇科癌症的主要死因，其最常见和最致命的类型是高级别浆液性卵巢癌（HGSC）。在分子水平上，近一半的 HGSC 表现出无效的同源 DNA 重组和通常由 BRCA1 和 BRCA2 基因突变引起的 DNA 损伤/修复途径失活的破坏。最近，BRCA1/2 突变的检测对于使用 PARP 抑制剂的 HGSC 患者在阳性辅助铂类化疗反应后复发的明确临床环境中的个性化治疗变得重要。基于区域肿瘤学家对患者的选择，我们试图验证对来自区域医院的归档福尔马林固定石蜡包埋 (FFPE) 活检材料进行 BRCA1/2 突变检测的可能性。在研究中我们使用了：a/ 97例送到我们实验室的FFPE肿瘤切除物，原先在地区科室档案中保存1-3年，检索原则上尽量包含非坏死性肿瘤组织， b/ 下一代测序 (NGS) 检测，涵盖 MiSeq（Illumina® 平台）和 c/ Sophia DDM® 生物信息学平台上 BRCA1/2 基因的所有已知突变。FFPE 样本处理后，有 5 例因基因组 DNA 数量不足而被排除。92 名患者样本的 NGS 分析的生物信息学结果表明基因 BRCA1/2 中有 17.39% 的致病突变和 32.61% 的潜在致病突变。总体而言，在患者队列中检测到 50% 的致病性和潜在致病性突变。我们系列中相对较高的 BRCA1/2 突变发生率可能受到各种指标的影响，包括基于辅助治疗反应的患者选择以及频率的区域或人群异质性。基于跨学科合作，使用主要处理并在不同实验室长期储存的档案活检材料，没有统一定义的分析前条件，可以识别可能对 PARP 抑制治疗有更好反应的 HGSC 患者。