Urinary TERT promoter mutations as non-invasive biomarkers for the comprehensive detection of urothelial cancer
Abstract
BACKGROUND: Recurrent mutations in the promoter of the telomerase reverse transcriptase (TERT) gene (C228T and C250T) detected in tumours and cells shed into urine of urothelial cancer (UC) patients are putative biomarkers for UC detection and monitoring. However, the possibility of detecting these mutations in cell-free circulating DNA (cfDNA) in blood and urine, or DNA from urinary exfoliated cells (cellDNA) with a single-gene sensitive assay has never been tested in a case-control setting. METHODS: We developed a single-plex assay (UroMuTERT) for the detection of low-abundance TERT promoter mutations. We tested 93 primary and recurrent UC cases and 94 controls recruited in France (blood, urine samples and tumours for the cases), and 50 primary UC cases and 50 controls recruited in Portugal (urinary exfoliated cell samples). We compared our assay with urine cytology. FINDINGS: In the French series, C228T or C250T were detected in urinary cfDNA or cellDNA in 81 cases (87·1%; 95% CI 78·6-93·2), and five controls (Specificity 94·7%; 95%CI 88·0-98·3), with 98·6% (95% CI 92·5-99·96) concordance in matched tumours. Detection rate in plasma cfDNA among cases was 7·1%. The UroMuTERT sensitivity was (i) highest for urinary cfDNA and cellDNA combined, (ii) consistent across primary and recurrent cases, tumour stages and grades, (iii) higher for low-risk non-muscle invasive UC (86·1%) than urine cytology (23·0%) (P < 0·0001) and (iv) 93·9% when combined with cytology. In the Portuguese series - the sensitivity and specificity for detection of UC with urinary cellDNA was 68·0% (95% CI 53·3-80·5) and 98·0% (95% CI 89·3-100·0). INTERPRETATION: TERT promoter mutations detected by the UroMuTERT assay in urinary DNA (cfDNA or cellDNA) show excellent sensitivity and specificity for the detection of UC, significantly outperforming that of urine cytology notably for detection of low-grade early stages UC. FUND: French Cancer League; French Foster Research in Molecular Biology and European Commission FP7 Marie Curie COFUND.
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BibTeX
@article{avogbe2026urinary,
title = {{Urinary TERT promoter mutations as non-invasive biomarkers for the comprehensive detection of urothelial cancer}},
author = {Patrice Hodonou Avogbe and Arnaud Manel and Emmanuel Vian and Geoffroy Durand and Nathalie Forey and Catherine Voegele and Maria Zvereva and Md Ismail Hosen and Sonia Meziani and Berengere de Tilly and Gilles Polo and Olesia Lole and Pauline Francois and Tiffany Myriam Delhomme and Christine Carreira and Sara Monteiro-Reis and Rui Henrique and Behnoush Abedi-Ardekani and Graham Byrnes and Matthieu Foll and Elisabete Weiderpass and James Mckay and Carmen Jeronimo and Ghislaine Scelo and Florence Le Calvez-Kelm},
journal = {EBioMedicine},
year = {2026},
month = oct,
doi = {10.1016/j.ebiom.2019.05.004},
url = {https://hal.science/hal-05842042v1},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Urinary TERT promoter mutations as non-invasive biomarkers for the comprehensive detection of urothelial cancer
AU - Patrice Hodonou Avogbe
AU - Arnaud Manel
AU - Emmanuel Vian
AU - Geoffroy Durand
AU - Nathalie Forey
AU - Catherine Voegele
AU - Maria Zvereva
AU - Md Ismail Hosen
AU - Sonia Meziani
AU - Berengere de Tilly
AU - Gilles Polo
AU - Olesia Lole
AU - Pauline Francois
AU - Tiffany Myriam Delhomme
AU - Christine Carreira
AU - Sara Monteiro-Reis
AU - Rui Henrique
AU - Behnoush Abedi-Ardekani
AU - Graham Byrnes
AU - Matthieu Foll
AU - Elisabete Weiderpass
AU - James Mckay
AU - Carmen Jeronimo
AU - Ghislaine Scelo
AU - Florence Le Calvez-Kelm
PY - 2026
DA - 2026/10/28
JO - EBioMedicine
DO - 10.1016/j.ebiom.2019.05.004
UR - https://hal.science/hal-05842042v1
AB - BACKGROUND: Recurrent mutations in the promoter of the telomerase reverse transcriptase (TERT) gene (C228T and C250T) detected in tumours and cells shed into urine of urothelial cancer (UC) patients are putative biomarkers for UC detection and monitoring. However, the possibility of detecting these mutations in cell-free circulating DNA (cfDNA) in blood and urine, or DNA from urinary exfoliated cells (cellDNA) with a single-gene sensitive assay has never been tested in a case-control setting. METHODS: We developed a single-plex assay (UroMuTERT) for the detection of low-abundance TERT promoter mutations. We tested 93 primary and recurrent UC cases and 94 controls recruited in France (blood, urine samples and tumours for the cases), and 50 primary UC cases and 50 controls recruited in Portugal (urinary exfoliated cell samples). We compared our assay with urine cytology. FINDINGS: In the French series, C228T or C250T were detected in urinary cfDNA or cellDNA in 81 cases (87·1%; 95% CI 78·6-93·2), and five controls (Specificity 94·7%; 95%CI 88·0-98·3), with 98·6% (95% CI 92·5-99·96) concordance in matched tumours. Detection rate in plasma cfDNA among cases was 7·1%. The UroMuTERT sensitivity was (i) highest for urinary cfDNA and cellDNA combined, (ii) consistent across primary and recurrent cases, tumour stages and grades, (iii) higher for low-risk non-muscle invasive UC (86·1%) than urine cytology (23·0%) (P < 0·0001) and (iv) 93·9% when combined with cytology. In the Portuguese series - the sensitivity and specificity for detection of UC with urinary cellDNA was 68·0% (95% CI 53·3-80·5) and 98·0% (95% CI 89·3-100·0). INTERPRETATION: TERT promoter mutations detected by the UroMuTERT assay in urinary DNA (cfDNA or cellDNA) show excellent sensitivity and specificity for the detection of UC, significantly outperforming that of urine cytology notably for detection of low-grade early stages UC. FUND: French Cancer League; French Foster Research in Molecular Biology and European Commission FP7 Marie Curie COFUND.
SN - 2352-3964
ER -