Pyrosequencing versus methylation-specific PCR for assessment of MGMT methylation in tumor and blood samples of glioblastoma patients

Circulating biomarkers in blood may provide an interesting alternative to risky tissue biopsies in the diagnosis and follow-up of glioblastoma patients. We have assessed MGMT methylation status in blood and tissue samples from unresected glioblastoma patients who had been included in the randomized...

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Bibliographic Details
Published in:Scientific reports 2019-07, Vol.9 (1), p.11125-12, Article 11125
Main Authors: Estival, Anna, Sanz, Carolina, Ramirez, Jose-Luis, Velarde, Jose Maria, Domenech, Marta, Carrato, Cristina, de las Peñas, Ramón, Gil-Gil, Miguel, Sepúlveda, Juan, Armengol, Roser, Cardiel, Isaac, Berrocal, Alfonso, Luque, Raquel, Herrero, Ana, Balana, Carmen
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Language:English
Subjects:
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Biomarkers - blood
Biomarkers - metabolism
Biopsy
Blood
Brain cancer
Brain Neoplasms - blood
Brain Neoplasms - metabolism
Brain research
Clinical medicine
Cytotoxicity
DNA methylation
DNA Methylation - physiology
DNA Modification Methylases - metabolism
DNA Repair Enzymes - metabolism
Female
Glioblastoma
Glioblastoma - blood
Glioblastoma - metabolism
Humanities and Social Sciences
Humans
Male
Medical prognosis
Methylation
Middle Aged
multidisciplinary
Oncology
Pathogenesis
Patients
Plasma
Polymerase Chain Reaction - methods
Radiation therapy
Science
Science (multidisciplinary)
Sensitivity and Specificity
Tissues
Tumor Suppressor Proteins - metabolism
Tumors
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Summary:Circulating biomarkers in blood may provide an interesting alternative to risky tissue biopsies in the diagnosis and follow-up of glioblastoma patients. We have assessed MGMT methylation status in blood and tissue samples from unresected glioblastoma patients who had been included in the randomized GENOM-009 trial. Paired blood and tissue samples were assessed by methylation-specific PCR (MSP) and pyrosequencing (PYR). After establishing the minimum PYR cut-off that could yield a significant difference in overall survival, we assessed the sensitivity, specificity, positive predictive value and negative predictive value (NPV) of the analyses. Methylation could be detected in cfDNA by both MSP and PYR but with low concordance with results in tissue. Sensitivity was low for both methods (31% and 38%, respectively), while specificity was higher for MSP in blood than for PYR in plasma (96% vs 76%) and NPV was similar (56 vs 57%). Concordance of results in tissue by MSP and PYR was 84.3% (P 
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-019-47642-2