FGFR3
 ,
 TERT
 and
 OTX1
 as a Urinary Biomarker Combination for Surveillance of Patients with Bladder Cancer in a Large Prospective Multicenter Study

Beukers, Willemien; Keur, Kirstin A. van der; Kandimalla, Raju; Vergouwe, Yvonne; Steyerberg, Ewout W.; Boormans, Joost L.; Jensen, Jørgen Bjerggaard; Lorente, José A.; Real, Francisco X.; Segersten, U.; Ørntoft, Torben F.; Malats, Núria; Malmström, Per‐Uno; Dyrskjøt, Lars; Zwarthoff, Ellen C.

doi:10.1016/j.juro.2016.12.096

Cited by 76 publications

(88 citation statements)

References 16 publications

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“…In the present study, FGFR3 mutations were predominantly seen in female patients in comparison to their male counterpart, which is in line with recent study . Older patients tend to harbor more FGFR3 mutation signifying that these mutations are preponderant in patients who are older than 50 years, though the difference was insignificant.…”

Section: Discussionsupporting

confidence: 92%

“…As a marker for risk of recurrence, a recent large multicenter study suggested that detection of FGFR3 mutation is possible not only in tumor samples but also in urine specimen. Thus, it signifies the potential of urinalysis as an optional diagnostic tool in low‐grade bladder tumors, and provides a means for early detection of nonmuscle invasive high‐grade tumors . Another study strongly supported the notion that FGFR3 mutations were associated with good prognosis and better overall survival in muscle invasive bladder cancer .…”

Section: Introductionmentioning

confidence: 79%

“…Identification of molecular marker capable of predicting the risk of recurrence or progression will certainly help in better clinical management of bladder cancer patients. Recent studies suggest that activating mutation in the FGFR3 gene is 1 of the most recurrent molecular aberrations currently known in bladder tumors and is linked with low recurrence and progression rate . Majority of FGFR3 mutations in bladder cancer are reported from patient samples in Western countries .…”

Section: Discussionmentioning

confidence: 99%

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Molecular investigation of FGFR3 gene mutation and its correlation with clinicopathological findings in Indian bladder cancer patients

Ahmad¹,

Mahal²,

Verma³

et al. 2018

Cancer Reports

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Background: Molecular alteration of FGFR3 gene is the most common genetic event currently known in bladder cancer. Notably, FGFR3 mutation has emerged as a promising molecular biomarker for recurrence, prognosis, and therapeutic target in bladder cancer. Aim:The present study explored the frequency and distribution pattern of FGFR3 mutation in 100 Indian bladder cancer patients.Methods and results: Exons 7, 10, and 15 were subjected to nested PCR followed by bidirectional sequencing of the PCR products. Overall, FGFR3 gene mutations were identified in 19 bladder cancer patients (19%, 19 of 100). Most of the mutations were noted in exon 7 (15%), followed by exon 10 (4%). All mutations detected were missense in nature affecting amino acids at codons 248, 249, and 373. The S249C mutations were the most recurrent mutation seen in exon 7, while Y373C was commonly observed in exon 10. In contrast to exons 7 and 10, no mutations were seen in exon 15 in this study. Females and older age patients tend to show increased frequency of FGFR3 mutations. Furthermore, FGFR3 mutations were more common in low pathological stage (6/20 pTa and 13/71 pT1) and low-grade tumors (13/46). This predominance in low-grade tumors were significantly high in comparison to high-grade tumor (P = .04). Likewise, FGFR3 mutations were significantly higher in well-differentiated tumors (32.6%, 14/43) in comparison to moderately differentiated tumors (11.3%, 5/44), and poorly differentiated tumor (0%, 0/13) (P = .007). No other association of FGFR3 with tumor size, necrosis, and variant histology was noted. Conclusions:The current study highlights the spectrum of FGFR3 mutation in Indian patients, and the data presented here are similar to those reported from across the globe.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Molecular investigation of FGFR3 gene mutation and its correlation with clinicopathological findings in Indian bladder cancer patients

Ahmad¹,

Mahal²,

Verma³

et al. 2018

Cancer Reports

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“…This is generally considered the most convenient specimen for BC diagnosis, since it is expected that bladder tumor cells that are directly shed into the urine descend to the pellet upon centrifugation [3,10,11]. However, the presence of 'background' DNA from normal cells makes the sensitive detection of hypermethylated DNA in urine pellet challenging, particularly in low-grade/-stage disease [11][12][13]. As cell-free DNA from urine supernatant is assumed to be enriched for tumor DNA, this appeared an interesting alternative for urine-based methylation analysis for BC diagnosis [8][9][10][11].…”

Section: Discussionmentioning

confidence: 99%

Comparative Analysis of Urine Fractions for Optimal Bladder Cancer Detection Using DNA Methylation Markers

Hentschel

Nieuwenhuijzen

Bosschieter

et al. 2020

Cancers

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DNA methylation analysis of full void urine and urine pellet seems promising for bladder cancer (BC) detection and surveillance. Urinary cell-free DNA from urine supernatant is now gaining interest for other molecular tests in BC. This study aims to evaluate which urine fraction is preferred for BC diagnosis using methylation markers: full void urine, urine pellet or supernatant. Methylation levels of nine markers were determined in the three urine fractions and correlated with their respective tumor tissues in BC patients and compared to controls. For all markers and marker panel GHSR/MAL, diagnostic performance was determined by calculating the area under the curve (AUC) of the respective receiver operating characteristic curves. For most of the markers, there was a significant correlation between the methylation levels in each of the urine fractions and the matched tumor tissues. Urine pellet was the most representative fraction. Generally, AUCs for BC diagnosis were comparable among the fractions. The highest AUC was obtained for GHSR/MAL in urine pellet: AUC 0.87 (95% confidence interval: 0.73–1.00), corresponding to a sensitivity of 78.6% and a specificity of 91.7%. Our results demonstrate that cellular and cell-free DNA in urine can be used for BC diagnosis by urinary methylation analysis. Based on our comparative analysis and for practical reasons, we recommend the use of urine pellet.

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“…Beukers et al investigated the role of FGFR3 and of the methylation genes TERT and OTX1 in 977 NMIBC patients [49]. The combination of the three assays detected 57% of Rec with a specificity of 59%.…”

Section: Urinary Biomarkers For the Surveillance Of Bladder Cancer Pamentioning

confidence: 99%

An up-to-date catalog of available urinary biomarkers for the surveillance of non-muscle invasive bladder cancer

et al. 2018

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FGFR3 , TERT and OTX1 as a Urinary Biomarker Combination for Surveillance of Patients with Bladder Cancer in a Large Prospective Multicenter Study

Cited by 76 publications

References 16 publications

Molecular investigation of FGFR3 gene mutation and its correlation with clinicopathological findings in Indian bladder cancer patients

Molecular investigation of FGFR3 gene mutation and its correlation with clinicopathological findings in Indian bladder cancer patients

Comparative Analysis of Urine Fractions for Optimal Bladder Cancer Detection Using DNA Methylation Markers

An up-to-date catalog of available urinary biomarkers for the surveillance of non-muscle invasive bladder cancer

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