Bladder cancer is considered heterogeneous diseases with two major subgroups: non-muscle- invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC). It is a major healthcare problem, and it is one of the leading causes of mortality worldwide. Genetic mutations are not only a cause for carcinogenesis but are also a way for treatment strategy. The present study aimed to investigate breast cancer (BRCA genes) tumor suppressor gene mutations in bladder cancer tissue and combined blood samples for patients who developed secondary tumor after or during trimodal therapy. Fresh tissue samples and their matched blood samples were collected from four patients with bladder cancer. The objective regions for the examined genes (BRCA1 and BRCA2) were sequenced using next-generation sequencing (NGS); generated BAM files were uploaded to the cloud-based Ionreporter server, and the Oncomine BRCA-specific plugin was used to analyze the paired normal and tumor sample for each patient using the default plugin parameters. Intronic BRCA1 mutation c.5050-104 C >T was reported among the four investigated bladder cancer patients, and three somatic mutations were reported as follows: two of them were found to be benign rs1064793056 and rs28897679 on the Clinivar database and one nonsense pathogenic variant rs80357006. BRCA 2 gene mutation reported an exonic synonymous mutation rs397507876 in the tissue and germline DNA. Patients were treated with trimodal; however, three bladder cancer patients who reported BRCA mutations developed secondary tumors. Identification of mutational BRCA changes in bladder cancer is a promising marker for better treatment strategy. Further studies are encouraged on a large cohort of bladder cancer patients to confirm our findings.

中文翻译：

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靶向二代测序对膀胱癌的影响：四例报告

膀胱癌被认为是具有两个主要亚组的异质性疾病：非肌肉浸润性膀胱癌 (NMIBC) 和肌肉浸润性膀胱癌 (MIBC)。它是一个主要的医疗保健问题，也是全球死亡的主要原因之一。基因突变不仅是致癌的原因，也是治疗策略的一种方式。本研究旨在调查膀胱癌组织中的乳腺癌（BRCA 基因）抑癌基因突变，并针对在三联疗法后或期间发生继发性肿瘤的患者进行联合血样。从四名膀胱癌患者收集新鲜组织样本及其匹配的血液样本。检测基因（BRCA1 和 BRCA2）的目标区域使用二代测序（NGS）进行测序；生成的 BAM 文件上传到基于云的 Ionreporter 服务器，Oncomine BRCA 特定插件用于使用默认插件参数分析每个患者的配对正常和肿瘤样本。在四名受调查的膀胱癌患者中报告了内含子 BRCA1 突变 c.5050-104 C >T，并且报告了三个体细胞突变如下：其中两个在 Clinivar 数据库中被发现是良性的 rs1064793056 和 rs28897679 和一个无意义的致病变异rs80357006。BRCA 2 基因突变报告了组织和种系 DNA 中的外显子同义突变 rs397507876。患者接受三联疗法；然而，三名报告 BRCA 突变的膀胱癌患者发展为继发性肿瘤。识别膀胱癌中的突变 BRCA 变化是更好的治疗策略的有希望的标志物。鼓励对大量膀胱癌患者进行进一步研究以证实我们的发现。