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 |
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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%. The data suggest that quantitative analysis of APC hypermethylation may serve as a biomarker of primary lung cancer. © 2004 Wiley‐Liss, Inc.</description><identifier>ISSN: 0020-7136</identifier><identifier>EISSN: 1097-0215</identifier><identifier>DOI: 10.1002/ijc.20196</identifier><identifier>PMID: 15146565</identifier><identifier>CODEN: IJCNAW</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>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</subject><ispartof>International journal of cancer, 2004-07, Vol.110 (5), p.751-755</ispartof><rights>Copyright © 2004 Wiley‐Liss, Inc.</rights><rights>2004 INIST-CNRS</rights><rights>Copyright 2004 Wiley-Liss, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3826-cac7eea042e64a74ce012c79d09ad08be459d404448d4379fcbb02b2a81d9cca3</citedby><cites>FETCH-LOGICAL-c3826-cac7eea042e64a74ce012c79d09ad08be459d404448d4379fcbb02b2a81d9cca3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fijc.20196$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fijc.20196$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>315,781,785,1418,27929,27930,45579,45580</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15860520$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15146565$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Grote, Hans J.</creatorcontrib><creatorcontrib>Schmiemann, Viola</creatorcontrib><creatorcontrib>Kiel, Sibylle</creatorcontrib><creatorcontrib>Böcking, Alfred</creatorcontrib><creatorcontrib>Kappes, Rainer</creatorcontrib><creatorcontrib>Gabbert, Helmut E.</creatorcontrib><creatorcontrib>Sarbia, Mario</creatorcontrib><title>Aberrant methylation of the adenomatous polyposis coli promoter 1A in bronchial aspirates from patients with suspected lung cancer</title><title>International journal of cancer</title><addtitle>Int J Cancer</addtitle><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.</description><subject>Adenomatous Polyposis Coli Protein - genetics</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>APC</subject><subject>Biological and medical sciences</subject><subject>Bronchoscopy</subject><subject>Carcinoma, Non-Small-Cell Lung - genetics</subject><subject>Carcinoma, Small Cell - genetics</subject><subject>Case-Control Studies</subject><subject>Cell Line, Tumor</subject><subject>cytology</subject><subject>DNA Methylation</subject><subject>Female</subject><subject>Humans</subject><subject>hypermethylation</subject><subject>lung cancer</subject><subject>Lung Neoplasms - genetics</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Pneumology</subject><subject>Polymerase Chain Reaction</subject><subject>Promoter Regions, Genetic</subject><subject>real‐time PCR</subject><subject>Retrospective Studies</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Sensitivity and Specificity</subject><subject>Tumors of the respiratory system and mediastinum</subject><issn>0020-7136</issn><issn>1097-0215</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0T2P1DAQBmALgbjloOAPIDcgUezdjON8lavVAYdOooE6mjgT1icnDraj07b8cnzsStAgKhfz6J2xXiFeI1whgLq29-ZKAbbVE7FBaOstKCyfik2ewbbGoroQL2K8B0AsQT8XF1iirsqq3Iifu55DoDnJidPh6ChZP0s_ynRgSQPPfqLk1ygX746LjzZK452VS_CTTxwk7qSdZR_8bA6WnKS42ECJoxwzkUsO5DlF-WDTQcY1LmwSD9Kt83dpaDYcXopnI7nIr87vpfj24ebr_tP27svH2_3ubmuKRlVbQ6ZmJtCKK021NgyoTN0O0NIATc-6bAcNWutm0EXdjqbvQfWKGhxaY6i4FO9Oufn2HyvH1E02GnaOZs4_7GpsiwKh_i_EusRS4SN8f4Im-BgDj90S7ETh2CF0j810uZnudzPZvjmHrv3Ewx95riKDt2dA0ZAbcynGxr9cU0GpILvrk3uwjo__3tjdft6fVv8CnCOnZQ</recordid><startdate>20040710</startdate><enddate>20040710</enddate><creator>Grote, Hans J.</creator><creator>Schmiemann, Viola</creator><creator>Kiel, Sibylle</creator><creator>Böcking, Alfred</creator><creator>Kappes, Rainer</creator><creator>Gabbert, Helmut E.</creator><creator>Sarbia, Mario</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley-Liss</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TO</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20040710</creationdate><title>Aberrant methylation of the adenomatous polyposis coli promoter 1A in bronchial aspirates from patients with suspected lung cancer</title><author>Grote, Hans J. ; Schmiemann, Viola ; Kiel, Sibylle ; Böcking, Alfred ; Kappes, Rainer ; Gabbert, Helmut E. ; Sarbia, Mario</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3826-cac7eea042e64a74ce012c79d09ad08be459d404448d4379fcbb02b2a81d9cca3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Adenomatous Polyposis Coli Protein - genetics</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>APC</topic><topic>Biological and medical sciences</topic><topic>Bronchoscopy</topic><topic>Carcinoma, Non-Small-Cell Lung - genetics</topic><topic>Carcinoma, Small Cell - genetics</topic><topic>Case-Control Studies</topic><topic>Cell Line, Tumor</topic><topic>cytology</topic><topic>DNA Methylation</topic><topic>Female</topic><topic>Humans</topic><topic>hypermethylation</topic><topic>lung cancer</topic><topic>Lung Neoplasms - genetics</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Pneumology</topic><topic>Polymerase Chain Reaction</topic><topic>Promoter Regions, Genetic</topic><topic>real‐time PCR</topic><topic>Retrospective Studies</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Sensitivity and Specificity</topic><topic>Tumors of the respiratory system and mediastinum</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Grote, Hans J.</creatorcontrib><creatorcontrib>Schmiemann, Viola</creatorcontrib><creatorcontrib>Kiel, Sibylle</creatorcontrib><creatorcontrib>Böcking, Alfred</creatorcontrib><creatorcontrib>Kappes, Rainer</creatorcontrib><creatorcontrib>Gabbert, Helmut E.</creatorcontrib><creatorcontrib>Sarbia, Mario</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>International journal of cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Grote, Hans J.</au><au>Schmiemann, Viola</au><au>Kiel, Sibylle</au><au>Böcking, Alfred</au><au>Kappes, Rainer</au><au>Gabbert, Helmut E.</au><au>Sarbia, Mario</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Aberrant methylation of the adenomatous polyposis coli promoter 1A in bronchial aspirates from patients with suspected lung cancer</atitle><jtitle>International journal of cancer</jtitle><addtitle>Int J Cancer</addtitle><date>2004-07-10</date><risdate>2004</risdate><volume>110</volume><issue>5</issue><spage>751</spage><epage>755</epage><pages>751-755</pages><issn>0020-7136</issn><eissn>1097-0215</eissn><coden>IJCNAW</coden><abstract>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.</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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