The analysis of cancer genomic alterations in circulating tumor DNA (ctDNA) is rapidly developing as a platform for biomarker in patients with solid tumors. Very recent data indicate advantages in assessing urine and plasma for the analysis of mutant-DNA in muscle invasive bladder cancer (NMIBC). Different potential applications of ctDNA analysis in patients with different bladder cancer disease states might be envisaged. The direct comparison of peripheral sample types revealed that urinary samples are enriched in mutant-DNA as compared to plasma. In NMIBC patients, due to tumor localization, urinary samples might be enriched in mutant-DNA, thus increasing the sensitivity of mutant-DNA detection and bringing urinary mutant-DNA one step closer to clinical application. Advances in molecular biology techniques have allowed a better understanding of the pathways involved in BC pathogenesis and heterogeneity. NMIBC and MIBC are largely believed to develop secondary to different molecular alterations (KDM6A and FGFR3, TP53 and KMT2D respectively). Comprehensive characterization of tumor-specific DNA isolated from urine in non-metastatic bladder cancer might help in investigating alterations involved in bladder pathogenesis at the DNA level and determining the sequence of mutations implicated in tumor development and progression.
Circulating tumor DNA (ctDNA) analysis has shown to have remarkable translational potential in many solid cancer (1). The application of ctDNA in bladder cancer represents an exciting opportunity for clinical impact and, despite recent efforts, remains relatively unexplored (6). The clinical utility of tumor-specific cell-free DNA in body fluids could be greater in bladder cancer due to the possibility of monitoring mutant-DNA in urine. While ctDNA has been well studied in plasma, little data have been published on the analysis of mutant-DNA in urine. Nonetheless, latest data demonstrate that mutant-DNA is detectable in both plasma and urine of bladder cancer patients and that urinary samples are enriched in mutant-DNA as compared to plasma in MIBC patients. We here propose to study the potential clinical applicability of urinary mutant-DNA in NMIBC patients. Findings from this study might provide evidence for a non-invasive urine-based biomarker which might help to reduce the need for cystoscopy and refine surveillance programs and risk stratification in patients with NMIBC. With the development of new technologies, it became possible to investigate alterations involved in bladder pathogenesis at the DNA level and distinct genomic alterations were identified in NMIBC and MIBC. We here propose to analyze urinary cell-free DNA from NMIBC and MIBC patients for the detection of known mutations, to determine the sequence of mutations implicated in tumor development and progression. These new insights might optimistically translate into better understanding of this heterogeneous disease and lead to improvement in patients outcome through better tailored treatments.
References:
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