Abstract 106P
Background
Urinary tumor DNA profiling is promising for the diagnosis, monitoring, and treatment stratification of bladder cancer. However, previous studies are mainly using a targeted panel next-generation sequencing (NGS) approach, which is limited to predefined genes and thus lacks comprehensiveness. Here, we apply the boosted whole-exome sequencing (WES) to urinary and tissue tumor DNA in muscle-invasive bladder cancer (MIBC) to comprehensively compare the mutation profiles in matched urine and tissue samples.
Methods
Matched tumor tissue, urine and peripheral blood mononuclear cells (PBMC) samples were collected from twenty MIBC patients. Nineteen tumor tissue, nineteen urine and twenty PBMC samples passed sample quality control were processed for NGS. PredicineWES+, an NGS assay with whole-exome coverage and boosted coverage in 600 cancer-related genes from the PredicineATLAS panel, was applied to tumor, urine and PBMC samples for mutation profiling. Mutation profiles of tumor tissue and urinary DNA were analyzed and compared.
Results
Mutation profiles of urinary and tissue tumor DNA were highly concordant across patients, with frequently mutated genes (TERT, TP53, KMT2D, ARID1A, PIK3CA, FGFR3, etc.) displaying comparable prevalence. Cancer cell fractions (CCFs) inferred from paired urine (2-52%) and tumor tissue (17-68%) showed significant difference (p < 0.05). Though CCFs in urine were relatively lower, more somatic mutations were detected in urine than in tumor tissue (p < 0.05). Clonal analysis suggested multiple subclones likely existed for patients with more mutations in urine than matched tissue samples.
Conclusions
This study demonstrates the effectiveness of urinary tumor DNA as a tissue surrogate for mutation profiling in MIBC at the whole-exome scale, supporting urine-based noninvasive molecular profiling in precision medicine for patients with bladder cancer. PredicineWES+ assay enables accurate detection of subclonal mutations from urine samples and enables the detection of urine-based personalized minimal residual diseases (MRD) in MIBC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Shanghai Jiao Tong University School of Medicine.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.