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Prognostic value of O6-methylguanine-DNA methyltransferase status in glioblastoma patients, assessed by five different methods

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Abstract

This multicenter study assesses the value of O6-methylguanine-DNA methyltransferase (MGMT) status for predicting overall survival in glioblastoma patients. Five methods are used, to identify the approach with the best prognostic value. Eighty-one tumors were obtained from patients with glioblastomas treated by surgery and radiotherapy with concomitant temozolomide (TMZ) followed by adjuvant TMZ. MGMT promoter methylation was assessed by qualitative methyl-specific polymerase chain reaction (MSP), semiquantitative methyl-specific polymerase chain reaction (SQ-MSP), and pyrosequencing, while MGMT expression was measured at the RNA level by quantitative real-time PCR (Q-RT-PCR) and at the protein level by immunohistochemistry (IHC). MGMT promoter methylation as evaluated by MSP, SQ-MSP, and pyrosequencing was significantly correlated with overall survival. The best predictive value was obtained by pyrosequencing of one specific CpG position. Overall survival was 14 and 25 months for patients with percentages of methylation below and above the median, respectively. In contrast, MGMT status determined by Q-RT-PCR and IHC showed little or no correlation with overall survival, respectively. These results confirm the prognostic value of MGMT promoter methylation in glioblastoma patients initially treated with TMZ. SQ-MSP allowed better discrimination than classical MSP, and pyrosequencing represented a good option.

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Acknowledgements

We thank M. T. Le Cabellec, M. Marty, and Céline Marquant for their invaluable technical assistance. Samples in Rennes were collected and stored by the Centre de Ressources Biologiques. M.S.N. Carpenter improved the English style.

Grant support

Cancéropôle Grand Ouest Réseau Gliome—France.

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Authors and Affiliations

  1. EA3805, 86021, Poitiers, France

    Lucie Karayan-Tapon & Joëlle Guilhot

  2. Université de Poitiers, 86021, Poitiers, France

    Lucie Karayan-Tapon, Michel Wager & Gaëlle Fromont

  3. CHU de Poitiers, 86021, Poitiers, France

    Lucie Karayan-Tapon, Joëlle Guilhot, Michel Wager & Gaëlle Fromont

  4. CRLCC Eugène Marquis, 35042, Rennes, France

    Véronique Quillien

  5. UMR 6061, Faculté de Médecine, 35043, Rennes, France

    Véronique Quillien

  6. CIC 802 INSERM, 86021, Poitiers, France

    Joëlle Guilhot

  7. Département Anatomo-Pathologie, CHU de Rennes, 35000, Rennes, France

    Stephan Saikali

  8. Plate-Forme Transcriptome OUEST-Genopole, 35000, Rennes, France

    Amandine Etcheverry

  9. Département de Neurochirurgie, CHU de Rennes, 35000, Rennes, France

    Abderrahmane Hamlat

  10. Service Anatomo-Pathologie, CHU de Nantes, 44093, Nantes, France

    Delphine Loussouarn

  11. CRLCC René Gauducheau, 44000, Nantes, France

    Loïc Campion & Mario Campone

  12. INSERM U892, IRTUN, 8 quai Moncousu, BP 70721, 44007, Nantes-Cédex 1, France

    Loïc Campion, François-Marie Vallette & Catherine Gratas-Rabbia-Ré

  13. Université de Nantes, 44000, Nantes, France

    Loïc Campion, François-Marie Vallette & Catherine Gratas-Rabbia-Ré

  14. Service Biochimie, CHU de Nantes, 44093, Nantes, France

    Catherine Gratas-Rabbia-Ré

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  1. Lucie Karayan-Tapon
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11060_2009_31_MOESM3_ESM.pdf

Fig. 1 a Representative pyrograms for three patients. The analyzed sequence is indicated at the top of each pyrogram. The degree of methylation for the five CpG positions is shown in squares. b Kaplan–Meier estimates of overall survival according to pyrosequencing for CpG sites 1, 2, 3, and 5 (PDF 63 kb)

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Karayan-Tapon, L., Quillien, V., Guilhot, J. et al. Prognostic value of O6-methylguanine-DNA methyltransferase status in glioblastoma patients, assessed by five different methods. J Neurooncol 97, 311–322 (2010). https://doi.org/10.1007/s11060-009-0031-1

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