Prognostic value of O6-methylguanine-DNA methyltransferase status in glioblastoma patients, assessed by five different methods.
This multicenter study assesses the value of O(6)-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.
Université de Poitiers, 86021 Poitiers, France.
Lucie
L
Karayan-Tapon
Véronique
V
Quillien
Joëlle
J
Guilhot
Michel
M
Wager
Gaëlle
G
Fromont
Stephan
S
Saikali
Amandine
A
Etcheverry
Abderrahmane
A
Hamlat
Delphine
D
Loussouarn
Loïc
L
Campion
Mario
M
Campone
François-Marie
FM
Vallette
Catherine
C
Gratas-Rabbia-Ré
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics / Q000378:metabolism*; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005909:Glioblastoma / Q000175:diagnosis* / Q000201:enzymology* / Q000401:mortality; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011336:Probability; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D013997:Time Factors; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes