Exome‐wide molecular insights from blood and urine liquid biopsies in genitourinary cancers

Abstract Background Liquid biopsy has emerged as a non‐invasive method for real‐time cancer monitoring especially in genitourinary (GU) oncology. Most current studies utilize a panel‐based molecular profiling ranging from 50–600 genes; however, a comprehensive exome‐wide profiling of real‐world patient samples has been lacking. Methods Over 2000 liquid biopsy samples were analyzed in this study, including urine samples from early‐stage bladder cancer and plasma samples from prostate, lung, breast, esophageal, head and neck cancers, among others. Cell‐free DNA (cfDNA) was extracted from these samples and analyzed using PredicineWES+™, a boosted comprehensive whole‐exome sequencing (WES) assay with an in‐depth coverage of 600 cancer‐related genes derived from the PredicineATLAS™ panel. Data analysis was conducted in‐house using Predicine's DeepSea bioinformatics software. Results The PredicineWES+™ assay demonstrated high sensitivity for detecting somatic mutations across the exome and showed comparable tumor mutational burden (TMB) estimates with the PredicineATLAS™ panel. Interestingly, the highest tumor TMB score was observed in bladder cancer among the analyzed cancers, which is consistent with literature using tissue‐based genomic profiling. The most common cancer variants include TP53 , ERBB2 , KRAS , PIK3CA , FGFR3 , APC , among others. Conclusion Liquid biopsy‐based genomic profiling across various cancer types provides an in‐depth analysis of biomarker discovery for personalized cancer care, setting the foundation for improved cancer diagnosis and personalized treatment strategies for urological diseases.