Implications of targeted next-generation sequencing for bladder cancer: report of four cases

• Main Authors: Mohamed K. Khalifa, Noha M. Bakr, Amal Ramadan, Khaled M. Abd Elwahab, Esam Desoky, Amira M. Nageeb, Menha Swellam
• Format: Article
• Language: English
• Published: SpringerOpen 2021-06-01
• Series: Journal of Genetic Engineering and Biotechnology
• Subjects: Bladder cancer; Somatic mutation; Germline mutation; BRCA genes; Next-generation sequencing; Case report
• Online Access: https://doi.org/10.1186/s43141-021-00182-7

Abstract Background 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. Results 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. Conclusion 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.