DNA-methylation profiling distinguishes malignant melanomas from benign nevi.
DNA-methylation profiling distinguishes malignant melanomas from benign nevi.
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DOI：
10.1111/j.1755-148x.2011.00828.x
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发表时间：
2011-04
影响因子：
4.3
通讯作者：
Thomas NE
中科院分区：
文献类型：
--
作者：
Conway K;Edmiston SN;Khondker ZS;Groben PA;Zhou X;Chu H;Kuan PF;Hao H;Carson C;Berwick M;Olilla DW;Thomas NE
DNA甲基化是一种表观遗传学改变，通常发生在癌症发展的早期，可能有助于黑色素瘤的分子诊断。我们确定了使用福尔马林固定的石蜡包埋组织进行高通量DNA甲基化阵列分析的技术可行性，以选择黑色素瘤和痣之间的候选DNA甲基化差异。使用1505 CpG位点微阵列对27例常见良性痣和22例原发性侵袭性黑色素瘤的启动子甲基化进行了评估。在调整了年龄、性别和多重比较后，发现22个基因的26个CpG位点的甲基化水平在黑色素瘤和痣之间存在显著差异，β值差异为≥0.2。微阵列的预测分析确定了12个对黑色素瘤具有高度预测性的CpG基因座，其受试者操作特征曲线下的面积为0.95。在我们的22个基因小组中，有14个基因在29个色素痣(包括发育不良的色素痣)和25个原发性侵袭性黑色素瘤的独立样本集中具有统计学意义，在调整了年龄、性别和多重比较后。首次报道了区分黑色素瘤和色素痣的DNA甲基化特征，这表明DNA甲基化似乎有望成为提高黑色素瘤诊断的另一种工具。
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.