Genomic Profiling Identified E606Q Mutation in Helicase Domain Respond to Platinum-Based Neoadjuvant Therapy in Urothelial Bladder Cancer.

Genomic profiling of tumors enables therapeutic decisions, and identifying drug-matched mutations will prolong survival and prognosis. Here, we generated a custom panel for detecting genetic alterations in 19 patients with urothelial bladder cancer. This panel targeted 71 genes associated with urological cancer. Targeted sequencing was performed on formalin-fixed paraffin-embedded tumor tissues. Paired patient-matched tumor and blood samples were subjected to this analysis. A total of 142 somatic mutations were detected in 19 tumor tissues. At least one non-synonymous mutation was detected in all tumor tissues, and , , , and were recurrently mutated. Chromatin remodeling and epigenetic modifier genes are frequently mutated. Of 142 mutations, 69 mutations (49%) were annotated to have oncogenic potential. Furthermore, 74% of patients were expected to receive targeted therapy due to drug-matched mutations being identified in their tumors. Among this cohort, a patient harbored an helicase domain mutation and would be expected to respond to platinum-based therapy. As expected, the patient received carboplatin-containing neoadjuvant therapy with a remarkable response. Furthermore, tumor-derived mutations in urine were rapidly decreased after neoadjuvant therapy. These results suggested targeted sequencing could help to detect drug-matched somatic mutations and indicate single or combination therapy for cancer patients.