DNA-methylation profiling distinguishes malignant melanomas from benign nevi.

Publisher: Blackwell Munksgaard Country of Publication: England NLM ID: 101318927 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1755-148X (Electronic) Linking ISSN: 17551471 NLM ISO Abbreviation: Pigment Cell Melanoma Res Subsets: MEDLINE

Original Publication: Oxford : Blackwell Munksgaard,

DNA Methylation*; Melanoma/*genetics ; Nevus/*genetics ; Skin Neoplasms/*genetics; Biomarkers, Tumor/genetics ; Epigenesis, Genetic ; Gene Expression Profiling ; Humans ; Melanoma/diagnosis ; Melanoma/pathology ; Nevus/diagnosis ; Nevus/pathology ; ROC Curve ; Skin Neoplasms/diagnosis ; Skin Neoplasms/pathology ; Tissue Array Analysis

DNA methylation, an epigenetic alteration typically occurring early in cancer development, could aid in the molecular diagnosis of melanoma. We determined technical feasibility for high-throughput DNA-methylation array-based profiling using formalin-fixed paraffin-embedded tissues for selection of candidate DNA-methylation differences between melanomas and nevi. Promoter methylation was evaluated in 27 common benign nevi and 22 primary invasive melanomas using a 1505 CpG site microarray. Unsupervised hierarchical clustering distinguished melanomas from nevi; 26 CpG sites in 22 genes were identified with significantly different methylation levels between melanomas and nevi after adjustment for age, sex, and multiple comparisons and with β-value differences of ≥ 0.2. Prediction analysis for microarrays identified 12 CpG loci that were highly predictive of melanoma, with area under the receiver operating characteristic curves of > 0.95. Of our panel of 22 genes, 14 were statistically significant in an independent sample set of 29 nevi (including dysplastic nevi) and 25 primary invasive melanomas after adjustment for age, sex, and multiple comparisons. This first report of a DNA-methylation signature discriminating melanomas from nevi indicates that DNA methylation appears promising as an additional tool for enhancing melanoma diagnosis.
(© 2011 John Wiley & Sons A/S.)

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P30 ES010126 United States ES NIEHS NIH HHS; R21 CA134368-02 United States CA NCI NIH HHS; T32 ES007126 United States ES NIEHS NIH HHS; R21CA134368 United States CA NCI NIH HHS; R21 CA134368-01A1 United States CA NCI NIH HHS; T32-5ES007126-27 United States ES NIEHS NIH HHS; R21 CA134368 United States CA NCI NIH HHS; P30ES010126 United States ES NIEHS NIH HHS

0 (Biomarkers, Tumor)

Date Created: 20110308 Date Completed: 20110624 Latest Revision: 20211020

20231215

PMC3073305

10.1111/j.1755-148X.2011.00828.x

21375697