Whole genome methylation profiles as independent markers of survival in stage IIIC melanoma patients.
Background: The clinical course of cutaneous melanoma (CM) can differ significantly for patients with identical stages of disease, defined clinico-pathologically, and no molecular markers differentiate patients with such a diverse prognosis. This study aimed to define the prognostic value of whole g...
| Publicado en: | Journal of Translational Medicine Vol. 10; no. 1; pp. 185 - 186 |
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| Autores principales: | , , , , , , , , , |
| Formato: | research Journal Article |
| Publicado: |
BioMed Central
2012
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=104307370&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 104307370 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 14795876 1CW3 jtl: Journal of Translational Medicine issn: 14795876 maglogo: N pubinfo: dt: 2012 vid: 10 iid: 1 pid: 24147 pub: BioMed Central artinfo: ui: 104307370 NLM22950745 2011923559 10.1186/1479-5876-10-185 NLM22950745 PMC3539917 104307370 ppf: 185 ppct: 1 formats: tig: atl: Whole genome methylation profiles as independent markers of survival in stage IIIC melanoma patients. aug: au: Sigalotti, Luca Covre, Alessia Fratta, Elisabetta Parisi, Giulia Sonego, Paolo Colizzi, Francesca Coral, Sandra Massarut, Samuele Kirkwood, John M Maio, Michele sug: subj: DNA Genome Melanoma Metabolism Survival Analysis Adult Aged Aged, 80 and Over Nucleotides DNA Probes Female Human Male Melanoma Pathology Middle Age Polymerase Chain Reaction Adult: 19-44 years Aged: 65+ years Aged, 80 & over Middle Aged: 45-64 years Female Male ab: Background: The clinical course of cutaneous melanoma (CM) can differ significantly for patients with identical stages of disease, defined clinico-pathologically, and no molecular markers differentiate patients with such a diverse prognosis. This study aimed to define the prognostic value of whole genome DNA methylation profiles in stage III CM.Methods: Genome-wide methylation profiles were evaluated by the Illumina Human Methylation 27 BeadChip assay in short-term neoplastic cell cultures from 45 stage IIIC CM patients. Unsupervised K-means partitioning clustering was exploited to sort patients into 2 groups based on their methylation profiles. Methylation patterns related to the discovered groups were determined using the nearest shrunken centroid classification algorithm. The impact of genome-wide methylation patterns on overall survival (OS) was assessed using Cox regression and Kaplan-Meier analyses.Results: Unsupervised K-means partitioning by whole genome methylation profiles identified classes with significantly different OS in stage IIIC CM patients. Patients with a "favorable" methylation profile had increased OS (P = 0.001, log-rank = 10.2) by Kaplan-Meier analysis. Median OS of stage IIIC patients with a "favorable" vs. "unfavorable" methylation profile were 31.5 and 10.4 months, respectively. The 5 year OS for stage IIIC patients with a "favorable" methylation profile was 41.2% as compared to 0% for patients with an "unfavorable" methylation profile. Among the variables examined by multivariate Cox regression analysis, classification defined by methylation profile was the only predictor of OS (Hazard Ratio = 2.41, for "unfavorable" methylation profile; 95% Confidence Interval: 1.02-5.70; P = 0.045). A 17 gene methylation signature able to correctly assign prognosis (overall error rate = 0) in stage IIIC patients on the basis of distinct methylation-defined groups was also identified.Conclusions: A discrete whole-genome methylation signature has been identified as molecular marker of prognosis for stage IIIC CM patients. Its use in daily practice is foreseeable, and promises to refine the comprehensive clinical management of stage III CM patients. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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