title: Prognostic relevance of SOCS3 hypermethylation in patients with glioblastoma multiforme.
abstract: 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.
authors.affiliation: Department of Pathology, Catholic University of Sacred Heart, Rome, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Martini
authors.forename: Roberto
authors.initials: R
authors.lastname: Pallini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Luongo
authors.forename: Tonia
authors.initials: T
authors.lastname: Cenci
authors.forename: Corrado
authors.initials: C
authors.lastname: Lucantoni
authors.forename: Luigi Maria
authors.initials: LM
authors.lastname: Larocca
mesh_terms: 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
chemical_list: 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