Clinical Significance of Hotspot Mutation Analysis of Urinary Cell-Free DNA in Urothelial Bladder Cancer

Fujita

et al. 2020

IJMS

Self Cite

Bladder cancer is the most common cancer of the urinary tract. Although nonmuscle-invasive bladder cancers have a good prognosis, muscle-invasive bladder cancers promote metastases and have a poor prognosis. Comprehensive analyses using RNA sequence of clinical tumor samples in bladder cancer have been reported. These reports implicated the candidate genes and pathways that play important roles in carcinogenesis and/or progression of bladder cancer. Further investigations for the function of each mutation are warranted. There is suggestive evidence for several environmental factors as risk factors of bladder cancer. Environmental factors such as cigarette smoking, exposure to chemicals and gases, bladder inflammation due to microbial and parasitic infections, diet, and nutrition could induce several genetic mutations and alter the tumor microenvironment, such as immune cells and fibroblasts. The detailed mechanism of how these environmental factors induce carcinogenesis and/or progression of bladder cancer remains unclear. To identify the relationship between the mutations and the lifestyle could be useful for prevention and treatment of bladder cancer.

Section: Representative Genetic Mutations In Bladder Cancermentioning

confidence: 99%

“…ERCC2 signature mutations were at higher levels in smokers than nonsmokers [ 30 ]. Fantoni F. et al reported molecular footprints of MIBCs in smoking and nonsmoking patients [ 57 ].…”

Section: Potential Effects Of Environmental Factors On Bladder Canmentioning

confidence: 99%

Mutational Landscape and Environmental Effects in Bladder Cancer

Fujita

et al. 2020

IJMS

Self Cite

“…These findings are in line with an initial study from 2007 reporting the superiority of urinary cfDNA over cellDNA for the detection of genetic alterations of patients with urothelial cancer [ 78 , 79 ]. Applied to the detection of the TERT promoter mutations, two recent studies highlighted the potential of the marker in urinary cfDNA for the detection of BC [ 80 , 81 ]. Specifically, of 77 patients whose tumor cells carried the 228 G > A/T mutation, the same mutation was detected by ddPCR in urinary cfDNA of 71 individuals (92%) and the mutation was absent in cfDNA of 26 of 27 healthy patients (specificity of 96%).…”

Section: Urinary Tert Promoter Mutations: the Hmentioning

confidence: 99%

Activating Telomerase TERT Promoter Mutations and Their Application for the Detection of Bladder Cancer

Zvereva

Pisarev

Hosen

et al. 2020

IJMS

This review summarizes state-of-the-art knowledge in early-generation and novel urine biomarkers targeting the telomerase pathway for the detection and follow-up of bladder cancer (BC). The limitations of the assays detecting telomerase reactivation are discussed and the potential of transcription-activating mutations in the promoter of the TERT gene detected in the urine as promising simple non-invasive BC biomarkers is highlighted. Studies have shown good sensitivity and specificity of the urinary TERT promoter mutations in case-control studies and, more recently, in a pilot prospective cohort study, where the marker was detected up to 10 years prior to clinical diagnosis. However, large prospective cohort studies and intervention studies are required to fully validate their robustness and assess their clinical utility. Furthermore, it may be interesting to evaluate whether the clinical performance of urinary TERT promoter mutations could increase when combined with other simple urinary biomarkers. Finally, different approaches for assessment of TERT promoter mutations in urine samples are presented together with technical challenges, thus highlighting the need of careful technological validation and standardization of laboratory methods prior to translation into clinical practice.

“…In combination with cytology, these mutations achieved a sensitivity of 78.6% and a specificity of 96.0% in diagnosis and staging of upper tract urothelial carcinoma [ 47 ]. In another study, these authors [ 48 ] evidenced that the diagnostic sensitivity of this strategy outperformed that of the combination of cytology and UroVysion, an FDA-approved assay to aid in BC diagnosis.…”

Section: Resultsmentioning

confidence: 99%

Circulating Cell-Free DNA in Liquid Biopsies as Potential Biomarker for Bladder Cancer: A Systematic Review

Herranz

Oto

Plana

et al. 2021

Cancers

Bladder cancer (BC) is among the most frequent cancer types in the world and is the most lethal urological malignancy. Presently, diagnostic and follow-up methods for BC are expensive and invasive. Thus, the identification of novel predictive biomarkers for diagnosis, progression, and prognosis of BC is of paramount importance. To date, several studies have evidenced that cell-free DNA (cfDNA) found in liquid biopsies such as blood and urine may play a role in the particular scenario of urologic tumors, and its analysis may improve BC diagnosis report about cancer progression or even evaluate the effectiveness of a specific treatment or anticipate whether a treatment would be useful for a specific patient depending on the tumor characteristics. In the present review, we have summarized the up-to-date studies evaluating the value of cfDNA as potential diagnostic, prognostic, or monitoring biomarker for BC in several biofluids.