DNA‐methylation profiling distinguishes malignant melanomas from benign nevi

Abstract

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.

Epigenetic signature of differentially methylated genes in cutaneous melanoma

“…Interestingly, although disclosed in a small cohort, this epigenetic signature was validated in a larger independent dataset of malignant melanomas from TCGA. Thomas and colleagues used a similar assay to investigate DNA methylation differences between CM and benign nevi [18]. The authors found 145 genes with significant DNA methylation differences between the two groups.…”

Biomarkers for Melanoma Diagnosis and the Technologies Used to Identify Them

“…It has been suggested that GPC3 may be a useful early stage biomarker for patients with the early stages of the disease (0 -II) (Nakatsura et al, 2004;Ikuta et al, 2005). Moreover, cyclooxygenase-2 (COX-2) (Chwirot and Kuźbicki, 2007), serum amyloid A (SAA) (Mian et al, 2005;Findeisen et al, 2009) and DNA methylation profiling (Conway et al, 2011) can be used to distinguish between early melanomas and benign nevi.…”

Genomics of Human Malignant Melanoma

“…The group's results have clearly identified a group of genes in a statistically powerful interpretation that can be used to discriminate nevi from melanomas considering their methylation signature. Furthermore, they adapted this highthroughput methylation profiling to FFPE samples, which are generally prepared by pathologists, abundantly available and appropriate for further routine screening [Conway et al, 2011].…”