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Article type: Research Article
Authors: Quillien, Véroniquea; b; * | Lavenu, Audreyc; d | Ducray, Françoise; f | Meyronet, Davide; f | Chinot, Olivierg | Fina, Frédérich | Sanson, Marci | Carpentier, Catherinei | Karayan-Tapon, Luciej; k | Rivet, Pierrek | Entz-Werle, Natachal; m | Legrain, Michèlel | Zalcman, Emmanuèle Lechaptn | Levallet, Guenaellen | Escande, Fabienneo | Ramirez, Caroleo | Chiforeanu, Danp | Vauleon, Elodiea; b | Figarella-Branger, Dominiqueg; q
Affiliations: [a] Centre Eugène Marquis, Rennes, France | [b] INSERM U1242, Université de Rennes 1, Rennes, France | [c] Faculté de Médecine, Université Rennes 1, Rennes, France | [d] INSERM CIC 0203, Université de Rennes 1, Rennes, France | [e] Hospices Civils de Lyon, Lyon, France | [f] Université de Lyon1, Villeurbanne, France | [g] CHU Timone, Marseille, France | [h] Faculté de Médecine Secteur Nord, Marseille, France | [i] INSERM CNRS, Sorbonne Universités UPMC Université Paris 06, Paris, France | [j] INSERM U1084, Université de Poitiers, Poitiers, France | [k] CHU de Poitiers, Poitiers, France | [l] CHRU Hautepierre, Strasbourg, France | [m] EA 3430, Progression Tumorale et Microenvironnement, Approches Translationnelles et Épidémiologie, Université de Strasbourg, Strasbourg, France | [n] CHU Caen, Département de Pathologie, Caen, France | [o] CHRU de Lille, Lille, France | [p] CHU de Rennes, Rennes, France | [q] INSERM U911 CRO2, Université de la Méditerranée, Marseille, France
Correspondence: [*] Corresponding author: Véronique Quillien, Centre Eugène Marquis, F-35042 Rennes, France. Tel.: +33 299 253 190; Fax: +33 299 253 164; E-mail: v.quillien@rennes.unicancer.fr.
Abstract: BACKGROUND: Pyrosequencing is recognized as a strong technique to analyze the MGMT status of glioblastoma patients. The most commonly used assay, quantifies the methylation levels of CpGs 74 to 78. A more recent CE-marked In Vitro Diagnostic Medical Device (CE-IVD) assay, Therascreen, analyzes CpGs 76–79. METHODS: We performed a comparison of these two assays to evaluate the potential impact of this shift in analyzed CpGs. Therascreen analysis was centrally performed for 102 glioblastoma patients, who were part of a prospective multicenter trial. RESULTS: A strong correlation was observed for the mean values of the 4 or 5 analyzed CpGs, with lower values recorded using the Therascreen assay, especially for values greater than 20%. When considering a classification in 3 categories (> 12%: methylated; ⩽ 8%: unmethylated; 9–12%: grey zone), 93% of patients were identically classified between the two assays. Using a binary classification, 95% and 97% of patients were identically classified with cut-offs of 8% and 12%, respectively. A strong prognostic significance was observed for both assays: median overall survival were 15.9 months and 34.9 months for respectively unmethylated and methylated patients with either test. CONCLUSION: The results demonstrate that these assays may be used interchangeably.
Keywords: Glioblastoma, MGMT methylation, pyrosequencing, CE-IVD kit
DOI: 10.3233/CBM-170191
Journal: Cancer Biomarkers, vol. 20, no. 4, pp. 435-441, 2017
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