Validation of the high-performance of pyrosequencing for clinical MGMT testing on a cohort of glioblastoma patients from a prospective dedicated multicentric trial - Université de Rennes Accéder directement au contenu
Article Dans Une Revue Oncotarget Année : 2016

Validation of the high-performance of pyrosequencing for clinical MGMT testing on a cohort of glioblastoma patients from a prospective dedicated multicentric trial

Olivier Chinot
Elodie Vauleon

Résumé

Background: The goal of this prospective multicentric trial was to validate a technique that allowed for MGMT promoter methylation analysis in routine clinical practice.Methods: The MGMT status of 139 glioblastoma patients, whom had received standard first line treatment, was determined using pyrosequencing (PSQ) and a semi-quantitative Methylation-specific PCR (sqMS-PCR) method, using both frozen and formalin-fixed paraffin-embedded FFPE samples. Eight participating centers locally performed the analysis, including external quality controls.Results: There was a strong correlation between results from FFPE and frozen samples. With cut-offs of 12% and 13%, 98% and 91% of samples were identically classified with PSQ and sqMS-PCR respectively. In 12% of cases frozen samples were excluded because they had a low percentage of tumor cells. In 5-6% of cases the analysis was not feasible on FFPE samples. The optimized risk cut-offs were higher in both techniques when using FFPE samples, in comparison to frozen samples. For sqMS-PCR, we validated a cut-off between 13-15% to dichotomize patients. For PSQ, patients with a low level of methylation (<= 8%) had a median progression-free survival under 9 months, as compared with more than 15.5 months for those with a level above 12%. For intermediate values (9-12%), more discordant results between FFPE and frozen samples were observed and there was not a clear benefit of temozolomide treatment, which indicated a “grey zone”.Conclusions: MGMT status can reliably be investigated in local laboratories. PSQ is the ideal choice as proven by strong interlaboratory reproducibility, along with threshold agreements across independent studies.

Domaines

Cancer
Fichier principal
Vignette du fichier
11322-171404-1-PB.pdf (3.85 Mo) Télécharger le fichier
Origine : Publication financée par une institution
Loading...

Dates et versions

hal-01358205 , version 1 (31-08-2016)

Identifiants

Citer

Véronique Quillien, Audrey Lavenu, François Ducray, Marie-Odile Joly, Olivier Chinot, et al.. Validation of the high-performance of pyrosequencing for clinical MGMT testing on a cohort of glioblastoma patients from a prospective dedicated multicentric trial. Oncotarget, 2016, 7 (38), pp.61916-61929. ⟨10.18632/oncotarget.11322⟩. ⟨hal-01358205⟩
298 Consultations
210 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More