1. Urinary TERT promoter mutations as non-invasive biomarkers for the comprehensive detection of urothelial cancerResearch in context
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Patrice Hodonou Avogbe, Arnaud Manel, Emmanuel Vian, Geoffroy Durand, Nathalie Forey, Catherine Voegele, Maria Zvereva, Md Ismail Hosen, Sonia Meziani, Berengere De Tilly, Gilles Polo, Olesia Lole, Pauline Francois, Tiffany Myriam Delhomme, Christine Carreira, Sara Monteiro-Reis, Rui Henrique, Behnoush Abedi-Ardekani, Graham Byrnes, Matthieu Foll, Elisabete Weiderpass, James McKay, Carmen Jeronimo, Ghislaine Scelo, and Florence Le Calvez-Kelm
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Medicine ,Medicine (General) ,R5-920 - 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
- Published
- 2019
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