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DNA‐methylation profiling distinguishes malignant melanomas from benign nevi
Author(s) -
Conway Kathleen,
Edmiston Sharon N.,
Khondker Zakaria S.,
Groben Pamela A.,
Zhou Xin,
Chu Haitao,
Kuan Pei Fen,
Hao Honglin,
Carson Craig,
Berwick Marianne,
Olilla David W.,
Thomas Nancy E.
Publication year - 2011
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/j.1755-148x.2011.00828.x
Subject(s) - dna methylation , melanoma , cpg site , methylation , epigenetics , dna microarray , biology , cancer research , pathology , medicine , gene , genetics , gene expression
Summary 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.