Clinical validation of a novel quantitative assay for the detection of MGMT methylation in glioblastoma patients
| العنوان: | Clinical validation of a novel quantitative assay for the detection of MGMT methylation in glioblastoma patients |
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| المؤلفون: | Olga Pernía, Sara Palacios-Zambrano, Itsaso Losantos-Garcia, Inmaculada Ibanez-de-caceres, Isabel Esteban, Darío Sanchez-Cabrero, Ismael Ghanem, Virginia Martínez-Marín, Rocío Rosas-Alonso, Carlos Rodriguez-Antolin, Julian Colmenarejo-Fernandez, Gema Moreno-Bueno, Javier de Castro |
| المساهمون: | UAM. Departamento de Bioquímica, Instituto de Salud Carlos III, European Commission |
| المصدر: | Clinical Epigenetics Digital.CSIC. Repositorio Institucional del CSIC instname Biblos-e Archivo. Repositorio Institucional de la UAM |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Oncology, Epigenomics, Male, Kaplan-Meier Estimate, Polymerase Chain Reaction, Cohort Studies, MGMT methylation, International harmonization, Prospective Studies, Promoter Regions, Genetic, DNA Modification Methylases, Genetics (clinical), Aged, 80 and over, Dp_qMSP, Brain Neoplasms, Middle Aged, Prognosis, Progression-Free Survival, Clinical Practice, Quantitative assay, Biomarker (medicine), Female, Mgmt methylation, Adult, medicine.medical_specialty, Medicina, Sensitivity and Specificity, Internal medicine, Genetics, medicine, Overall survival, Biomarkers, Tumor, Temozolomide, Humans, Progression-free survival, Molecular Biology, neoplasms, Antineoplastic Agents, Alkylating, Aged, business.industry, Research, MSP, Tumor Suppressor Proteins, DNA Methylation, medicine.disease, DNA Repair Enzymes, ROC Curve, CpG Islands, business, Glioblastoma, Developmental Biology |
| الوصف: | © The Author(s) 2021. [Background]: The promoter hypermethylation of the methylguanine-DNA methyltransferase gene is a frequently used biomarker in daily clinical practice as it is associated with a favorable prognosis in glioblastoma patients treated with temozolamide. Due to the absence of adequately standardized techniques, international harmonization of the MGMT methylation biomarker is still an unmet clinical need for the diagnosis and treatment of glioblastoma patients. [Results]: In this study we carried out a clinical validation of a quantitative assay for MGMT methylation detection by comparing a novel quantitative MSP using double-probe (dp_qMSP) with the conventional MSP in 100 FFPE glioblastoma samples. We performed both technologies and established the best cutoff for the identification of positive-methylated samples using the quantitative data obtained from dp_qMSP. Kaplan–Meier curves and ROC time dependent curves were employed for the comparison of both methodologies. [Conclusions]: We obtained similar results using both assays in the same cohort of patients, in terms of progression free survival and overall survival according to Kaplan–Meier curves. In addition, the results of ROC(t) curves showed that dp_qMSP increases the area under curve time-dependent in comparison with MSP for predicting progression free survival and overall survival over time. We concluded that dp_qMSP is an alternative methodology compatible with the results obtained with the conventional MSP. Our assay will improve the therapeutic management of glioblastoma patients, being a more sensitive and competitive alternative methodology that ensures the standardization of the MGMT-biomarker making it reliable and suitable for clinical use. This study was supported by the “Fondo de Investigación Sanitaria-Instituto de Salud Carlos III” PI18/00050, DTS20/00029 and the European Regional Development Fund/European Social Fund FIS FEDER/FSE, Una Manera de Hacer Europa. |
| وصف الملف: | application/pdf |
| تدمد: | 1868-7083 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5d0c2cde520cada429a8c44b04fcaba1Test https://pubmed.ncbi.nlm.nih.gov/33750464Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....5d0c2cde520cada429a8c44b04fcaba1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 18687083 |
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