2404P - Concordance of genomic alterations by next-generation sequencing in tumor tissue versus urinary tumor DNA and circulating tumor DNA in bladder cancer

Background

The current gold standard for diagnosing and monitoring bladder cancer is cystoscopy, but its application is restricted due to invasiveness and high cost. Liquid biopsy has gained widespread attention recently because of its non-invasive, convenient access, and convenient for real-time monitoring. This study aimed to explore the consistency of genomic alterations of bladder cancer detected by urine and blood with their paired tissue to evaluate the potential of liquid biopsy in the real world.

Methods

For this analysis, we included 20 bladder cancer patients with all their tissue, blood, and urine samples. The next-generation sequencing technology was used to detect the mutated genes of 60 obtained samples via the Acornmed panel with 808 cancer-related genes. The average sequencing depth was >10,000x, and the coverage was 95%.

Results

A total of 60 samples from 20 patients were tested in this study. In 90% (18/20) of patients, at least one concordance mutation was detected in both tissue DNA and urinary tumor DNA(utDNA), while at least one concordance mutation was detected in both ctDNA and tDNA in 80% (16/20) of patients. A total of 357 mutated genes were detected in all tissue samples, and 202 mutated genes were detected in all urine samples, of which 179 (88.6%) genes were also detected in tissue DNA. A total of 148 mutated genes were detected in all blood samples, of which 109 (73.6%) genes were also detected in tissue DNA. A total of 75 genes were detected in the three samples, of which 12 (16%) were clinically available genes that could be found in the OncoKB database. The Top 5 frequently mutated genes in tDNA were TERT (50%), TP53 (45%), FAT (35%), LRP1B (35%), and PIK3CA (30%), whereas the Top 5 mutant genes detected in utDNA were TERT (40%), TP53 (30%), KMT2D (25%), NOTCH4 (20%), and PIK3CA (15%), in ctDNA were ATRX (15%), IRS2 (15%), NOTCH4 (15%), ZFHX3 (15%), and KMT2D (10%).

Conclusions

Results of this study show that liquid biopsies represented by urine and blood overlap with the genomic results of tissues, suggesting that utDNA and ctDNA may have potential applications in patients with bladder cancer who have no tumor tissue available, offering similar profiles of genomic alterations of tumor tissues.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.