Epigenetic Profiles Distinguish Pleural Mesothelioma from Normal Pleura and Predict Lung Asbestos Burden and Clinical Outcome
Epigenetic Profiles Distinguish Pleural Mesothelioma from Normal Pleura and Predict Lung Asbestos Burden and Clinical Outcome
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DOI：
10.1158/0008-5472.can-08-2586
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发表时间：
2009-01-01
期刊：
影响因子：
11.2
通讯作者：
Kelsey, Karl T.
中科院分区：
文献类型：
--
作者：
Christensen, Brock C.;Houseman, E. A.;Kelsey, Karl T.
石棉等非致突变致癌物的作用机制仍未得到很好的描述。由于已知胸膜间皮瘤的基因突变数量有限，我们的目标是描述这种快速致命的石棉相关肿瘤中基因特定甲基化改变、疾病状态、石棉负担和生存之间的关系。对158例胸膜间皮瘤和18例正常胸膜组织中与803个癌相关基因相关的1505个CpG基因座的甲基化进行了研究。经误发率校正后，969个CpG基因座与疾病状态独立相关(q<；0.05)。用混合模型方法根据CpG甲基化特征对样本进行分类，甲基化类别区分肿瘤和正常胸膜(排列P<；0.0001)。在随机森林分类中，总体错误分类错误率为3.4%，
Mechanisms of action of nonmutagenic carcinogens such as asbestos remain poorly characterized. As pleural mesothelioma is known to have limited numbers of genetic mutations, we aimed to characterize the relationships among gene-locus-specific methylation alterations, disease status, asbestos burden, and survival in this rapidly fatal asbestos-associated tumor. Methylation of 1505 CpG loci associated with 803 cancer-related genes were studied in 158 pleural mesotheliomas and 18 normal pleura. After false-discovery rate correction, 969 CpG loci were independently associated with disease status (Q < 0.05). Classifying samples based on CpG methylation profile with a mixture model approach, methylation classes discriminated tumor from normal pleura (permutation P < 0.0001). In a random forests classification, the overall misclassification error rate was 3.4%, with