REPEATABILITY OF CANCER MUTATION DETECTION IN URINE LIQUID BIOPSY: MORE SAMPLES ARE BETTER

Abstract

Introduction

Single urine samples are the standard for cytology examination of urothelial tumors. The detection of urothelial cancer mutations in urine is an emerging research field, but there is currently no evidence-based standard for the timing or frequency of sampling. Our primary objective was to investigate the repeatability of urothelial cancer mutations in urine samples of bladder cancer patients. Our secondary objective was to refine a panel of bladder cancer-associated genes for future diagnostic research.

Methods

Urine samples from 39 bladder cancer patients were sequenced using a 127-gene panel. The Wilcoxon signed rank sum test was used to compare one urine sample versus multiple samples from the same patient with respect to mutation presence. For panel refinement, genes were considered if they were mutated in at least three patients of our cohort and confirmed by literature.

Results

Somatic mutation presence in a single urine sample is incomplete compared to several samples (V=120, p=.0005843). Our refined set of 32 genes enabled bladder cancer- associated mutation detection in all 39 patients (100%). The mutational landscape was congruent with literature.

Conclusions

More than one urine sample is needed to discover the mutational landscape in most bladder cancer patients, speculatively due to physiological or circadian reasons. Our refined set of 32 genes is probably sufficient for bladder cancer-associated mutation detection, even in a single sample. Urine-based mutation detection is promising for bladder cancer diagnostics and management, especially when multiple urine samples are used.