title: Methylation levels of the "long interspersed nucleotide element-1" repetitive sequences predict survival of melanoma patients.
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).
  
  
  CONCLUSIONS
  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.
authors: Cancer Bioimmunotherapy Unit, Centro di Riferimento Oncologico, Istituto di Ricovero e Cura a Carattere Scientifico, Aviano, Italy.
authors: Luca
authors: L
authors: Sigalotti
authors: Elisabetta
authors: E
authors: Fratta
authors: Ettore
authors: E
authors: Bidoli
authors: Alessia
authors: A
authors: Covre
authors: Giulia
authors: G
authors: Parisi
authors: Francesca
authors: F
authors: Colizzi
authors: Sandra
authors: S
authors: Coral
authors: Samuele
authors: S
authors: Massarut
authors: John M
authors: JM
authors: Kirkwood
authors: Michele
authors: M
authors: Maio
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