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Int. J. Mol. Sci. 2014, 15(7), 11984-11995; doi:10.3390/ijms150711984

Association of TNFRSF10D DNA-Methylation with the Survival of Melanoma Patients

1
Department of Dermatology and Venereology, Innsbruck Medical University, Innsbruck 6020, Austria
2
Department of Obstetrics and Gynecology, Innsbruck Medical University, Innsbruck 6020, Austria
3
Department of Medical Statistics, Informatics and Health Economics, Innsbruck Medical University, Innsbruck 6020, Austria
4
Oncotyrol, Center for Personalized Cancer Medicine, Innsbruck 6020, Austria
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Received: 1 May 2014 / Revised: 30 June 2014 / Accepted: 1 July 2014 / Published: 7 July 2014
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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Abstract

In this retrospective pilot study, the DNA-methylation status of genes that have been demonstrated to be involved in melanoma carcinogenesis was analyzed in order to identify novel biomarkers for the risk assessment of melanoma patients. We analyzed DNA extracted from punch-biopsies from 68 formalin-fixed paraffin-embedded (FFPE) melanoma specimens. Using MethyLight PCR, we examined 20 genes in specimens from a training set comprising 36 melanoma patients. Selected candidate genes were validated in a test set using FFPE tissue samples from 32 melanoma patients. First, we identified the TNFRSF10D DNA-methylation status (TNFRSF10D methylated vs. unmethylated) as a prognostic marker for overall (p = 0.001) and for relapse-free survival (p = 0.008) in the training set. This finding was confirmed in the independent test set (n = 32; overall survival p = 0.041; relapse-free survival p = 0.012). In a multivariate Cox-regression analysis including all patients, the TNFRSF10D DNA-methylation status remained as the most significant prognostic parameter for overall and relapse-free survival (relative-risk (RR) of death, 4.6 (95% CI: 2.0–11.0; p < 0.001), RR of relapse, 7.2 (95% CI: 2.8–18.3; p < 0.001)). In this study, we demonstrate that TNFRSF10D DNA-methylation analysis of a small tissue-punch from archival FFPE melanoma tissue is a promising approach to provide prognostic information in patients with melanoma. View Full-Text
Keywords: cancer biomarker; epigenomics; DNA-methylation; prognosis; translational cancer research cancer biomarker; epigenomics; DNA-methylation; prognosis; translational cancer research
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MDPI and ACS Style

Ratzinger, G.; Mitteregger, S.; Wolf, B.; Berger, R.; Zelger, B.; Weinlich, G.; Fritsch, P.; Goebel, G.; Fiegl, H. Association of TNFRSF10D DNA-Methylation with the Survival of Melanoma Patients. Int. J. Mol. Sci. 2014, 15, 11984-11995.

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