Promoter hypermethylation of resected bronchial margins: A field defect of changes?

Mingzhou Guo, Michael House, Craig Hooker, Yu Han, Elizabeth Heath, Edward Gabrielson, Stephen C. Yang, Stephen B. Baylin, James G. Herman, Malcolm V. Brock

Research output: Contribution to journalArticle

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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, SOCSI, RASSFIA, COX2, and RARβ 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 hypermethylation abnormalities are also present in the primary tumor and thus may represent a field defect of preneoplastic changes that occurs early in carcinogenesis.

Original languageEnglish (US)
Pages (from-to)5131-5136
Number of pages6
JournalClinical Cancer Research
Volume10
Issue number15
DOIs
StatePublished - Aug 1 2004
Externally publishedYes

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Methylation
Neoplasms
Recurrence
Non-Small Cell Lung Carcinoma
Epigenomics
Neoplasm Metastasis
Genes
DNA Methylation
Carcinogenesis
Research Design
Polymerase Chain Reaction
Lung
Survival
DNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Promoter hypermethylation of resected bronchial margins : A field defect of changes? / Guo, Mingzhou; House, Michael; Hooker, Craig; Han, Yu; Heath, Elizabeth; Gabrielson, Edward; Yang, Stephen C.; Baylin, Stephen B.; Herman, James G.; Brock, Malcolm V.

In: Clinical Cancer Research, Vol. 10, No. 15, 01.08.2004, p. 5131-5136.

Research output: Contribution to journalArticle

Guo, M, House, M, Hooker, C, Han, Y, Heath, E, Gabrielson, E, Yang, SC, Baylin, SB, Herman, JG & Brock, MV 2004, 'Promoter hypermethylation of resected bronchial margins: A field defect of changes?', Clinical Cancer Research, vol. 10, no. 15, pp. 5131-5136. https://doi.org/10.1158/1078-0432.CCR-03-0763
Guo, Mingzhou ; House, Michael ; Hooker, Craig ; Han, Yu ; Heath, Elizabeth ; Gabrielson, Edward ; Yang, Stephen C. ; Baylin, Stephen B. ; Herman, James G. ; Brock, Malcolm V. / Promoter hypermethylation of resected bronchial margins : A field defect of changes?. In: Clinical Cancer Research. 2004 ; Vol. 10, No. 15. pp. 5131-5136.
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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, SOCSI, RASSFIA, COX2, and RARβ 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 hypermethylation abnormalities are also present in the primary tumor and thus may represent a field defect of preneoplastic changes that occurs early in carcinogenesis.",
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AU - Guo, Mingzhou

AU - House, Michael

AU - Hooker, Craig

AU - Han, Yu

AU - Heath, Elizabeth

AU - Gabrielson, Edward

AU - Yang, Stephen C.

AU - Baylin, Stephen B.

AU - Herman, James G.

AU - Brock, Malcolm V.

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N2 - 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, SOCSI, RASSFIA, COX2, and RARβ 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 hypermethylation abnormalities are also present in the primary tumor and thus may represent a field defect of preneoplastic changes that occurs early in carcinogenesis.

AB - 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, SOCSI, RASSFIA, COX2, and RARβ 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 hypermethylation abnormalities are also present in the primary tumor and thus may represent a field defect of preneoplastic changes that occurs early in carcinogenesis.

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