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Promoter hypermethylation of resected bronchial margins: a field defect of changes?
| Content Provider | Semantic Scholar |
|---|---|
| Author | Guo, Mingzhou House, Michael G. Hooker, Craig M. Han, Yu Ling Heath, Elizabeth I. Gabrielson, Edward W. Yang, Stephen Chi-Tin Baylin, Stephen B. Herman, James G. Brock, Malcolm V. |
| Copyright Year | 2004 |
| Abstract | PURPOSE Histologically positive bronchial margins after resection for non-small cell lung cancer are associated with shortened patient survival due to local recurrence. We hypothesized that DNA promoter hypermethylation changes at bronchial margins could be detected in patients with no histological evidence of malignancy and that they would reflect epigenetic events in the primary tumor. EXPERIMENTAL DESIGN Bronchial margins, primary tumor, bronchoalveolar fluid, and paired nonmalignant lung were obtained from 20 non-small cell lung cancer patients who underwent a lobectomy or greater resection. Disease-specific recurrence was the primary end point. The methylation status of p16, MGMT, DAPK, SOCS1, RASSF1A, COX2, and RARbeta was examined using methylation-specific polymerase chain reaction. RESULTS All malignancies had methylation in at least one locus. Concordance of one gene with an identical epigenetic change in the tumor or bronchial margin was observed in 85% of patients. Only one patient had methylation at the bronchial margin for a gene that was not methylated in the corresponding tumor. Median time to recurrence was 37 months (range, 5-71 months). There were two local recurrences and five metastases. There were no significant correlations between DNA methylation in tumor, margins, or bronchoalveolar fluid specimens and either regional recurrence or distant metastases. CONCLUSIONS Histologically negative bronchial margins of resected non-small cell lung cancer exhibit frequent hypermethylation changes in multiple genes. These hyper-methylation abnormalities are also present in the primary tumor and thus may represent a field defect of preneoplastic changes that occurs early in carcinogenesis. |
| Starting Page | 1 |
| Ending Page | 6 |
| Page Count | 6 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://clincancerres.aacrjournals.org/content/clincanres/10/15/5131.full.pdf |
| PubMed reference number | 15297416v1 |
| Volume Number | 10 |
| Issue Number | 15 |
| Journal | Clinical cancer research : an official journal of the American Association for Cancer Research |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Carcinogenesis Congenital Abnormality DAPK1 gene Epigenetic Process Excision Hyperactive behavior Hypermethylation Methylation Neoplasm Metastasis Neoplasms Non-Small Cell Lung Carcinoma Patients Polymerase Chain Reaction RASSF1 gene Recurrence (disease attribute) Small cell carcinoma of lung Specimen Structure of parenchyma of lung lobectomy primary tumor study of epigenetics |
| Content Type | Text |
| Resource Type | Article |