Posted: Thursday, April 6, 2023
A recent article published in Scientific Reports highlighted the use of mutation hotspots in noncoding regions of specific genes as potential biomarkers for bladder cancer detection. D.G. Ward, MD, MPH, of the University of Birmingham, United Kingdom, and colleagues examined urine samples of patients with and without bladder cancer to identify variants in noncoding regions across groups. Their findings revealed that noncoding mutations were readily detectable in the urine of patients with bladder cancer but were undetectable or present at much lower frequencies in patients without bladder cancer.
A total of 884 urine cell pellet DNA samples were examined in this study. A subset of samples (142) from patients without bladder cancer were used to optimize variant calling, and massively parallel sequencing was used to identify the noncoding hotspots across the different patient groups. Other samples included 591 from patients treated at a hematuria clinic (165 bladder cancer, 426 non–bladder cancer) and 293 from patients with non–muscle-invasive bladder cancer who were undergoing surveillance. After DNA sequencing, the data were demultiplexed and used to build consensus reads.
Overall findings revealed that mutations were detected far more commonly in urine cell pellet DNA samples from patients with bladder cancer compared with patients without bladder cancer (P < .001). Additionally, the median calculated maximum variant allele frequency was significantly higher in bladder cancer recurrence urine cell pellet DNA samples than in nonrecurrent samples (3.32% vs. 0.81%, P < .001). Other findings indicated that noncoding mutations were used to detect incident bladder cancer with a sensitivity of 66% (95% confidence interval [CI] = 58%–75%) and a specificity of 92% (95% CI = 88%–95%).
Based on these findings, the study authors concluded that “noncoding hotspot mutations behave similarly to driver mutations in bladder cancer–associated genes and could be included in biomarker panels for bladder cancer detection.”
Disclosure: For full disclosures of the study authors, visit nature.com.