Urine DNA for monitoring chemoradiotherapy response in muscle‐invasive bladder cancer: a pilot study

Gordon, Naheema S.; Baxter, Laura; Goel, Ankit; Arnold, Roland; Kaur, Baljit; Liu, Wenyu; Pirrie, Sarah; Hussain, Syed A.; Viney, Richard; Ford, Daniel; Zarkar, Anjali; Wood, M. C.; Mitin, Timur; Thompson, Reid F.; James, Nicholas D.; Ward, Douglas G.; Bryan, Richard T.

doi:10.1111/bju.15589

Cited by 3 publications

(3 citation statements)

References 8 publications

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“…All the above studies illustrate that urinary DNA markers perform well in the detection and surveillance of BLCA. Several studies analysed changes in BLCA‐associated DNA mutations in the urine of patients with MIBC before, during and after treatment with chemotherapy or chemoradiotherapy and suggested that measuring tumour‐specific DNA mutations in urine might be a valuable tool for monitoring treatment response 124,125 . However, whether urinary DNA markers could contribute to monitoring treatment responses in patients with BLCA remains to be further evaluated.…”

Section: Opportunities Of Urine‐based Liquid Biopsy In Blcamentioning

confidence: 99%

Urine‐based liquid biopsy in bladder cancer: Opportunities and challenges

Wang

Jin

et al. 2023

Clinical and Translational Dis

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Bladder cancer (BLCA) is a most common urological tumours with high rate of recurrence, which needs long‐term of follow‐up. To date, diagnosis and surveillance of BLCA still rely on cystoscopy, an invasive and expensive method that increases the difficulty for routine follow‐up. Therefore, exploring new biomarkers or tests is an effective way to improve the current clinical management of BLCA. Recent years, liquid biopsy has received increasing attention, especially for its great potential for clinical application in the non‐invasive detection of tumours. In addition, liquid biopsy involves a wide range of biomarkers, including DNA, RNA, proteins, extracellular vesicles and metabolites in blood, urine or other body fluids. For BLCA, urine is a most ideal body fluid to achieve non‐invasive diagnosis and surveillance. Here, we address recent developments of urine‐based biomarkers or tests for clinical diagnostic challenges in BLCA, such as early detection, minimal residual, recurrence monitoring and therapeutic response. Meanwhile, the many challenges of urine biomarkers that need to be overcome are also discussed.

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Section: Opportunities Of Urine‐based Liquid Biopsy In Blcamentioning

confidence: 99%

Urine‐based liquid biopsy in bladder cancer: Opportunities and challenges

Wang

Jin

et al. 2023

Clinical and Translational Dis

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“…Two studies have examined PLEKHS1 and TBC1D12 mutations in the urine of BC patients and non-cancer control subjects; however, both had limited samples sizes and used healthy controls 11,12 . The variant allele frequencies of the non-coding hotspots in urine have also been shown to decrease following chemoradiotherapy in BC patients and following upper-tract tumour resection 13,14 .Multiple studies have shown that coding mutations in BC-associated genes and the TERT promoter can be used for the non-invasive detection of BC 11,15,16 . We hypothesized that non-coding mutation hotspots may also…”

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confidence: 99%

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confidence: 99%

Properties of non-coding mutation hotspots as urinary biomarkers for bladder cancer detection

Baxter

Gordon²,

Ott³

et al. 2023

Sci Rep

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Mutations at specific hotspots in non-coding regions of ADGRG6, PLEKHS1, WDR74, TBC1D12 and LEPROTL1 frequently occur in bladder cancer (BC). These mutations could function as biomarkers for the non-invasive detection of BC but this remains largely unexplored. Massively-parallel sequencing of non-coding hotspots was applied to 884 urine cell pellet DNAs: 591 from haematuria clinic patients (165 BCs, 426 non-BCs) and 293 from non-muscle invasive BC surveillance patients (29 with recurrence). Urine samples from 142 non-BC haematuria clinic patients were used to optimise variant calling. Non-coding mutations are readily detectable in the urine of BC patients and undetectable, or present at much lower frequencies, in the absence of BC. The mutations can be used to detect incident BC with 66% sensitivity (95% CI 58–75) at 92% specificity (95% CI 88–95) and recurrent disease with 55% sensitivity (95% CI 36–74) at 85% specificity (95% CI 80–89%) using a 2% variant allele frequency threshold. In the NMIBC surveillance setting, the detection of non-coding mutations in urine in the absence of clinically detectable disease was associated with an increased relative risk of future recurrence (RR = 4.62 (95% CI 3.75–5.48)). As urinary biomarkers, non-coding hotspot mutations behave similarly to driver mutations in BC-associated genes and could be included in biomarker panels for BC detection.

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Circulating and urinary tumour DNA in urothelial carcinoma — upper tract, lower tract and metastatic disease

et al. 2023

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Urine DNA for monitoring chemoradiotherapy response in muscle‐invasive bladder cancer: a pilot study

Abstract: Accumulating evidence implies the utility of DNA-based urine biomarkers for initial detection of bladder cancer (BC) and surveillance of non-muscle-invasive BC [1,2]. We have

Cited by 3 publications

References 8 publications

Urine‐based liquid biopsy in bladder cancer: Opportunities and challenges

Urine‐based liquid biopsy in bladder cancer: Opportunities and challenges

Properties of non-coding mutation hotspots as urinary biomarkers for bladder cancer detection

Circulating and urinary tumour DNA in urothelial carcinoma — upper tract, lower tract and metastatic disease

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