MGMT methylation assessment in glioblastoma: MS-MLPA versus human methylation 450K beadchip array and immunohistochemistry

S. Trabelsi; N. Mama; M. Ladib; N. Karmeni; M. Haddaji Mastouri; M. Chourabi; M. Mokni; K. Tlili; H. Krifa; M. T. Yacoubi; A. Saad; D. H mida Ben Brahim

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MGMT methylation assessment in glioblastoma: MS-MLPA versus human methylation 450K beadchip array and immunohistochemistry

S. Trabelsi ^[2] ; N. Mama ^[1] ; M. Ladib ^[1] ; N. Karmeni ^[1] ; M. Haddaji Mastouri ^[2] ; M. Chourabi ^[2] ; M. Mokni ^[2] ; K. Tlili ^[1] ; H. Krifa ^[1] ; M. T. Yacoubi ^[2] ; A. Saad ^[2] ; D. H mida Ben Brahim ^[2]
1. [1] Hôpital Sahloul
  
  Hôpital Sahloul
  
  Túnez
2. [2] Farhat Hached University Hospital, Túnez
Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 18, Nº. 4 (April 2016), 2016, págs. 391-397
Idioma: inglés
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Resumen
- Purpose The MGMT gene encodes a DNA repair enzyme that counteracts with chemotherapy efficiency, specifically with alkylating agents such as temozolomide (TMZ). It is well established that MGMT methylation should be screened as a predictive marker for TMZ in glioblastoma, and we thus aimed to determine a reliable and practical diagnostic method of MGMT methylation detection.
  
  Patients and methods 55 glioblastomas were investigated for MGMT methylation status using methylation-specific multiplexed ligation probe amplification (MS-MLPA), illumina human methylation 450K BeadChip array (HM450 K) analysis, and compared to MGMT protein expression by immunohistochemistry (IHC) staining. The methylation status of promoter, intron and all MGMT CpG targeted sites were separately correlated to patient’s survival.
  
  Results In addition to MS-MLPA and 450 K concordance, our results showed significantly higher overall survival (OS) of patients receiving TMZ and presenting MGMT methylated promoter (mean OS = 21.5 months, p = 0.046). Including all glioblastoma cases and regardless of chemotherapy, MS-MLPA showed significant survival difference between MGMT methylated and unmethylated cases (mean OS = 13, p = 0.021).
  
  Conclusion We concluded that in glioblastoma, MGMT promoter methylation predicts TMZ sensitivity. This current comparative analysis leads to consider that MS-MLPA is a valuable as HM450 K array for MGMT methylation status screening.