期刊
PIGMENT CELL & MELANOMA RESEARCH
卷 24, 期 2, 页码 352-360出版社
WILEY
DOI: 10.1111/j.1755-148X.2011.00828.x
关键词
melanoma; nevi; methylation profiling; diagnostic markers
资金
- National Cancer Institute [R21CA134368]
- Lineberger Comprehensive Cancer Center (LCCC) at the University of North Carolina at Chapel Hill
- National Institute of Environmental Health Sciences [P30ES010126]
- LCCC Biostatistics Core
- [T32-5ES007126-27]
P>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 beta-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.
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