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Journal of Neuro-Oncology

, Volume 97, Issue 3, pp 311–322 | Cite as

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

  • Lucie Karayan-Tapon
  • Véronique Quillien
  • Joëlle Guilhot
  • Michel Wager
  • Gaëlle Fromont
  • Stephan Saikali
  • Amandine Etcheverry
  • Abderrahmane Hamlat
  • Delphine Loussouarn
  • Loïc Campion
  • Mario Campone
  • François-Marie Vallette
  • Catherine Gratas-Rabbia-Ré
Laboratory Investigation - Human/Animal Tissue

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.

Keywords

MGMT methylation Temozolomide Glioblastoma Overall survival 

Notes

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.

Supplementary material

11060_2009_31_MOESM1_ESM.pdf (20 kb)
(PDF 20 kb)
11060_2009_31_MOESM2_ESM.pdf (22 kb)
(PDF 22 kb)
11060_2009_31_MOESM3_ESM.pdf (62 kb)
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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Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Lucie Karayan-Tapon
    • 1
    • 2
    • 3
  • Véronique Quillien
    • 4
    • 5
  • Joëlle Guilhot
    • 1
    • 3
    • 6
  • Michel Wager
    • 2
    • 3
  • Gaëlle Fromont
    • 2
    • 3
  • Stephan Saikali
    • 7
  • Amandine Etcheverry
    • 8
  • Abderrahmane Hamlat
    • 9
  • Delphine Loussouarn
    • 10
  • Loïc Campion
    • 11
    • 12
    • 13
  • Mario Campone
    • 11
  • François-Marie Vallette
    • 12
    • 13
  • Catherine Gratas-Rabbia-Ré
    • 12
    • 13
    • 14
  1. 1.PoitiersFrance
  2. 2.Université de PoitiersPoitiersFrance
  3. 3.CHU de PoitiersPoitiersFrance
  4. 4.CRLCC Eugène MarquisRennesFrance
  5. 5.UMR 6061, Faculté de MédecineRennesFrance
  6. 6.CIC 802 INSERMPoitiersFrance
  7. 7.Département Anatomo-PathologieCHU de RennesRennesFrance
  8. 8.Plate-Forme Transcriptome OUEST-GenopoleRennesFrance
  9. 9.Département de NeurochirurgieCHU de RennesRennesFrance
  10. 10.Service Anatomo-PathologieCHU de NantesNantesFrance
  11. 11.CRLCC René GauducheauNantesFrance
  12. 12.INSERM U892, IRTUNNantes-Cédex 1France
  13. 13.Université de NantesNantesFrance
  14. 14.Service BiochimieCHU de NantesNantesFrance

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