Aberrant methylation of the adenomatous polyposis coli promoter 1A in bronchial aspirates from patients with suspected lung cancer

Promoter hypermethylation is a major mechanism for gene silencing and offers a promising starting point for developing molecular biomarkers. The purpose of our study was to determine aberrant methylation of the adenomatous polyposis coli (APC) gene promoter 1A with respect to its prevalence and quan...

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Veröffentlicht in:International journal of cancer 2004-07, Vol.110 (5), p.751-755
Hauptverfasser: Grote, Hans J., Schmiemann, Viola, Kiel, Sibylle, Böcking, Alfred, Kappes, Rainer, Gabbert, Helmut E., Sarbia, Mario
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container_issue 5
container_start_page 751
container_title International journal of cancer
container_volume 110
creator Grote, Hans J.
Schmiemann, Viola
Kiel, Sibylle
Böcking, Alfred
Kappes, Rainer
Gabbert, Helmut E.
Sarbia, Mario
description Promoter hypermethylation is a major mechanism for gene silencing and offers a promising starting point for developing molecular biomarkers. The purpose of our study was to determine aberrant methylation of the adenomatous polyposis coli (APC) gene promoter 1A with respect to its prevalence and quantitative level in bronchial aspirates from patients with suspected lung cancer. Applying quantitative methylation‐specific PCR, 155 bronchial aspirates from patients with non‐small cell cancer (NSCLC) and small cell cancer (SCLC) of the lung as well as 67 bronchial aspirates from patients diagnosed for nonneoplastic lung disease were examined in a retrospective case‐control study. Aberrant APC promoter 1A methylation was seen in 71% of NSCLCs, 38% of SCLCs and 42% of patients with nonneoplastic lung disease, being therefore not specific for the presence of primary lung cancer. In contrast, quantitative analysis showed a significantly higher methylation level of bronchial aspirates from NSCLC as compared to patients without neoplastic lung disease. Introducing a cutoff point that defined high level of APC hypermethylation NSCLC could be discriminated from cases without neoplastic disease with a specificity of 98.5% and a sensitivity of 39%. The data suggest that quantitative analysis of APC hypermethylation may serve as a biomarker of primary lung cancer. © 2004 Wiley‐Liss, Inc.
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The purpose of our study was to determine aberrant methylation of the adenomatous polyposis coli (APC) gene promoter 1A with respect to its prevalence and quantitative level in bronchial aspirates from patients with suspected lung cancer. Applying quantitative methylation‐specific PCR, 155 bronchial aspirates from patients with non‐small cell cancer (NSCLC) and small cell cancer (SCLC) of the lung as well as 67 bronchial aspirates from patients diagnosed for nonneoplastic lung disease were examined in a retrospective case‐control study. Aberrant APC promoter 1A methylation was seen in 71% of NSCLCs, 38% of SCLCs and 42% of patients with nonneoplastic lung disease, being therefore not specific for the presence of primary lung cancer. In contrast, quantitative analysis showed a significantly higher methylation level of bronchial aspirates from NSCLC as compared to patients without neoplastic lung disease. Introducing a cutoff point that defined high level of APC hypermethylation NSCLC could be discriminated from cases without neoplastic disease with a specificity of 98.5% and a sensitivity of 39%. 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Introducing a cutoff point that defined high level of APC hypermethylation NSCLC could be discriminated from cases without neoplastic disease with a specificity of 98.5% and a sensitivity of 39%. 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Introducing a cutoff point that defined high level of APC hypermethylation NSCLC could be discriminated from cases without neoplastic disease with a specificity of 98.5% and a sensitivity of 39%. The data suggest that quantitative analysis of APC hypermethylation may serve as a biomarker of primary lung cancer. © 2004 Wiley‐Liss, Inc.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>15146565</pmid><doi>10.1002/ijc.20196</doi><tpages>5</tpages></addata></record>
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subjects Adenomatous Polyposis Coli Protein - genetics
Adult
Aged
Aged, 80 and over
APC
Biological and medical sciences
Bronchoscopy
Carcinoma, Non-Small-Cell Lung - genetics
Carcinoma, Small Cell - genetics
Case-Control Studies
Cell Line, Tumor
cytology
DNA Methylation
Female
Humans
hypermethylation
lung cancer
Lung Neoplasms - genetics
Male
Medical sciences
Middle Aged
Pneumology
Polymerase Chain Reaction
Promoter Regions, Genetic
real‐time PCR
Retrospective Studies
Reverse Transcriptase Polymerase Chain Reaction
Sensitivity and Specificity
Tumors of the respiratory system and mediastinum
title Aberrant methylation of the adenomatous polyposis coli promoter 1A in bronchial aspirates from patients with suspected lung cancer
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