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.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6603852 | PMC |
| http://dx.doi.org/10.1016/j.ebiom.2019.05.004 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Microbial Astaxanthin Synthesis by through Metabolic and Fermentation Engineering.
J Agric Food Chem
January 2025
State Key Laboratory of Materials-Oriented Chemical Engineering, College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing 211800, P.R. China.
Astaxanthin is a kind of carotenoid with a strong antioxidant ability, which has shown broad applications in the areas of healthcare, medicine, cosmetics, food additives, and aquaculture. With the increasing demand for natural products, the microbial production of astaxanthin has become a new hot spot. In this study, the astaxanthin synthesis pathway was first metabolically constructed in ()().
View Article and Find Full Text PDFPotentially actionable molecular alterations in particular related to poor oncologic outcomes in salivary gland carcinomas.
BMC Cancer
January 2025
Department of Tumor Biology and Genetics, Medical University of Warsaw, Warsaw, Poland.
Aim: The study was designed to evaluate molecular alterations, relevant to the prognosis and personalized therapy of salivary gland cancers (SGCs).
Materials And Methods: DNA was extracted from archival tissue of 40 patients with various SGCs subtypes. A targeted next-generation sequencing (NGS) panel was used for the identification of small-scale mutations, focal and chromosomal arm-level copy number changes.
Complex immunohistochemical and molecular study on 5 cases of ovarian juvenile granulosa cell tumors reveals a consistent alteration in the PI3K/AKT/mTOR signaling pathway.
Diagn Pathol
January 2025
Department of Pathology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Studničkova 2, Prague, 12800, Czech Republic.
Background: Juvenile granulosa cell tumor (JGCT) of the ovary is a rare tumor with distinct clinicopathological and hormonal features primarily affecting young women and children. We conducted a complex clinicopathological, immunohistochemical, and molecular analysis of five cases of JGCT.
Methods: The immunohistochemical examination was performed with 32 markers, including markers that have not been previously investigated.
Predictive and Prognostic Significance of Molecular Biomarkers in Glioblastoma.
Biomedicines
November 2024
Department of Neurosurgery, University of Florida, Gainesville, FL 32608, USA.
Glioblastoma multiforme (GBM), a WHO grade 4 glioma, is the most common and aggressive primary brain tumor, characterized by rapid progression and poor prognosis. The heterogeneity of GBM complicates diagnosis and treatment, driving research into molecular biomarkers that can offer insights into tumor behavior and guide personalized therapies. This review explores recent advances in molecular biomarkers, highlighting their potential to improve diagnosis and treatment outcomes in GBM patients.
View Article and Find Full Text PDFClinical Utility of Serial Circulating Tumor DNA Analysis as a Minimally Invasive Biomarker in Advanced Urothelial Cancer.
JCO Precis Oncol
January 2025
Department of Urology, Kyoto University School of Medicine, Kyoto, Japan.
Purpose: Circulating tumor DNA (ctDNA) analysis is an alternative to tissue biopsy for genotyping in various cancers. We aimed to establish a plasma ctDNA sequencing assay, then evaluate its clinical utility in advanced urothelial cancer (UC).
Materials And Methods: This study included 82 patients with muscle-invasive or metastatic UC.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!