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| Content Provider | PubMed Central |
|---|---|
| Author | Christensen, Brock C. Houseman, E. A. Godleski, John J. Marsit, Carmen J. Longacker, Jennifer L. Roelofs, Cora R. Karagas, Margaret R. Wrensch, Margaret R. Yeh, Ru-fang Nelson, Heather H. Wiemels, Joe L. Zheng, Shichun Wiencke, John K. Bueno, Raphael Sugarbaker, David J. Kelsey, Karl T. |
| Abstract | Mechanisms of action of non-mutagenic 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 upon 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 <1% (n=1) of tumors misclassified as normal (P < 0.0001). Among tumors, methylation class membership was significantly associated with lung tissue asbestos body burden (P < 0.03), and significantly predicted survival (likelihood ratio P < 0.01). Consistent with prior work, asbestos burden was associated with an increased risk of death (HR = 1.4, 95% CI, 1.1 – 1.8). Our results have shown that methylation profiles powerfully differentiate diseased pleura from non-tumor pleura and that asbestos burden and methylation profiles are independent predictors of mesothelioma patient survival. We have added to the growing body of evidence that cellular epigenetic dysregulation is a critical mode of action for asbestos in the induction of pleural mesothelioma. Importantly, these findings hold great promise for using epigenetic profiling in the diagnosis and prognosis of human cancers. |
| Related Links | http://dx.doi.org/10.1158/0008-5472.can-08-2586 |
| Ending Page | 234 |
| Page Count | 8 |
| Starting Page | 227 |
| File Format | |
| ISSN | 00085472 |
| e-ISSN | 15387445 |
| Journal | Cancer research |
| Issue Number | 1 |
| Volume Number | 69 |
| Language | English |
| Publisher Date | 2009-01-01 |
| Access Restriction | Open |
| Subject Keyword | Cancer Research Oncology Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cancer Research Oncology |
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