Properties of non-coding mutation hotspots as urinary biomarkers for bladder cancer detection.
Date
2023-01-19ICR Author
Author
Baxter, L
Gordon, NS
Ott, S
Wang, J
Patel, P
Goel, A
Piechocki, K
Silcock, L
Sale, C
Zeegers, MP
Cheng, KK
James, ND
BladderPath trial management group,
Bryan, RT
Ward, DG
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
Humans
Hematuria
Biomarkers, Tumor
Urinary Bladder Neoplasms
Urinary Bladder
Mutation
RNA-Binding Proteins
Research team
Prostate & Bladder Cancer
Language
eng
Date accepted
2023-01-05
License start date
2023-01-19
Citation
Scientific Reports, 2023, 13 (1), pp. 1060 -
Publisher
NATURE PORTFOLIO