Prognostic relevance of SOCS3 hypermethylation in patients with glioblastoma multiforme.
Alterations in the signal transduction pathways are key mechanisms in the pathogenesis of de novo glioblastoma multiforme (GBM), which are also involved in the resistance to chemo- and radiotherapy. Here, we analyzed the methylation status and mRNA expression of suppressor of cytokine signaling (SOCS)1-2-3, 3 of the most important inhibitory molecules of the signal transduction circuitry, in 46 GBM specimens. The relationship between methylation status of SOCS1-2-3 and clinical outcome was investigated. Using methylation-specific PCR (MS-PCR) and sequencing, after bisulphite modification, we found that the promoter of SOCS1-2-3 was methylated in 24, 6.5 and 35% of GBM, respectively. Real-time analysis showed that in methylated GBM, mRNA expression for SOCS1-2-3 was reduced by 5, 3 and 7-folds, respectively, when compared with unmethylated GBM. Moreover, methylation of SOCS3 promoter significantly associated with an unfavorable clinical outcome (p < 0.0002). Our data suggest that methylation of SOCS3 may be involved in the pathogenesis of GBM and in the resistance of this neoplasm to conventional treatment.
Martini
Maurizio
M
Department of Pathology, Catholic University of Sacred Heart, Rome, Italy.
Pallini
Roberto
R
Luongo
Giuseppe
G
Cenci
Tonia
T
Lucantoni
Corrado
C
Larocca
Luigi Maria
LM
D000328:Adult; D000368:Aged; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000378:metabolism; D045643:DNA Repair Enzymes / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism
D012333:RNA, Messenger; C108944:SOCS1 protein, human; C106643:SOCS2 protein, human; C106644:SOCS3 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes