Methylation levels of the "long interspersed nucleotide element-1" repetitive sequences predict survival of melanoma patients

Sigalotti, L and Fratta, E and Bidoli, E and Covre, A and Parisi, G and Colizzi, F and Coral, S and Massarut, S and Kirkwood, JM and Maio, M (2011) Methylation levels of the "long interspersed nucleotide element-1" repetitive sequences predict survival of melanoma patients. Journal of Translational Medicine, 9.

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Abstract

Background: The prognosis of cutaneous melanoma (CM) differs for patients with identical clinico-pathological stage, and no molecular markers discriminating the prognosis of stage III individuals have been established. Genome-wide alterations in DNA methylation are a common event in cancer. This study aimed to define the prognostic value of genomic DNA methylation levels in stage III CM patients.Methods: Overall level of genomic DNA methylation was measured using bisulfite pyrosequencing at three CpG sites (CpG1, CpG2, CpG3) of the Long Interspersed Nucleotide Element-1 (LINE-1) sequences in short-term CM cultures from 42 stage IIIC patients. The impact of LINE-1 methylation on overall survival (OS) was assessed using Cox regression and Kaplan-Meier analysis.Results: Hypomethylation (i.e., methylation below median) at CpG2 and CpG3 sites significantly associated with improved prognosis of CM, CpG3 showing the strongest association. Patients with hypomethylated CpG3 had increased OS (P = 0.01, log-rank = 6.39) by Kaplan-Meyer analysis. Median OS of patients with hypomethylated or hypermethylated CpG3 were 31.9 and 11.5 months, respectively. The 5 year OS for patients with hypomethylated CpG3 was 48% compared to 7% for patients with hypermethylated sequences. Among the variables examined by Cox regression analysis, LINE-1 methylation at CpG2 and CpG3 was the only predictor of OS (Hazard Ratio = 2.63, for hypermethylated CpG3; 95% Confidence Interval: 1.21-5.69; P = 0.01).Conclusion: LINE-1 methylation is identified as a molecular marker of prognosis for CM patients in stage IIIC. Evaluation of LINE-1 promises to represent a key tool for driving the most appropriate clinical management of stage III CM patients. © 2011 Sigalotti et al; licensee BioMed Central Ltd.

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Details

Item Type:	Article
Status:	Published
Creators/Authors:	Creators Email Pitt Username ORCID Sigalotti, L Fratta, E Bidoli, E Covre, A Parisi, G Colizzi, F Coral, S Massarut, S Kirkwood, JM kirkwood@pitt.edu KIRKWOOD Maio, M
Date:	26 May 2011
Date Type:	Publication
Journal or Publication Title:	Journal of Translational Medicine
Volume:	9
DOI or Unique Handle:	10.1186/1479-5876-9-78
Schools and Programs:	School of Medicine > Medicine
Refereed:	Yes
Date Deposited:	28 Oct 2016 18:48
Last Modified:	01 Nov 2017 12:56
URI:	http://d-scholarship.pitt.edu/id/eprint/30057

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