Detection of Promoter Hypermethylation of Multiple Genes in the Tumor and Bronchoalveolar Lavage of Patients with Lung Cancer
Purpose: Aberrant promoter hypermethylation of several known or putative tumor suppressor genes occurs frequently during the pathogenesis of lung cancers and is a promising marker for cancer detection. We investigated the feasibility of detecting aberrant DNA methylation in the bronchoalveolar lavag...
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| Veröffentlicht in: | Clinical cancer research 2004-04, Vol.10 (7), p.2284-2288 |
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| creator | TOPALOGLU, Ozlem HOQUE, Mohammad Obaidul TOKUMARU, Yutaka LEE, Juna RATOVITSKI, Edward SIDRANSKY, David MOON, Chul-So |
| description | Purpose: Aberrant promoter hypermethylation of several known or putative tumor suppressor genes occurs frequently during the pathogenesis
of lung cancers and is a promising marker for cancer detection. We investigated the feasibility of detecting aberrant DNA
methylation in the bronchoalveolar lavage (BAL) samples of lung cancer patients.
Experimental Design: We examined the tumor and the matched BAL DNA for aberrant methylation of eight gene promoters ( CDH1 , APC , MGMT , RASSF1A , GSTP1 , p16 , RAR-β2 , and ARF ) from 31 patients with primary lung tumors by quantitative fluorogenic real-time PCR. BAL from 10 age-matched noncancer patients
was used as a control.
Results: Promoter hypermethylation of at least one of the genes studied was detected in all 31 lung primary tumors; 27 (87%) CDH1 , 17 (55%) APC , 14 (45%) RASSF1A , 12 (39%) MGMT , 7 (23%) p16 , 3 (10%) GSTP1 , 3 (10%) RAR-β2 , and 0 (0%) ARF . Methylation was detected in CDH1 (48%), APC (29%), RASSF1A (29%), MGMT (58%), p16 (14%), GSTP1 (33%), RAR-β2 (0%), and ARF (0%) of BAL samples from matched methylation-positive primary tumors, and in every case, aberrant methylation in BAL DNA
was accompanied by methylation in the matched tumor samples. BAL samples from 10 controls without evidence of cancer revealed
no methylation of the MGMT , GSTP1 , p16 , ARF , or RAR-β2 genes whereas methylation of RASSF1 , CDH1 , and APC was detected at low levels. Overall, 21 (68%) of 31 BAL samples from cancer patients were positive for aberrant methylation.
Conclusion: Our findings suggest that promoter hypermethylation in BAL can be detected in the majority of lung cancer patients. This
approach needs to be evaluated in large early detection and surveillance studies of lung cancer. |
| doi_str_mv | 10.1158/1078-0432.CCR-1111-3 |
| format | Article |
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of lung cancers and is a promising marker for cancer detection. We investigated the feasibility of detecting aberrant DNA
methylation in the bronchoalveolar lavage (BAL) samples of lung cancer patients.
Experimental Design: We examined the tumor and the matched BAL DNA for aberrant methylation of eight gene promoters ( CDH1 , APC , MGMT , RASSF1A , GSTP1 , p16 , RAR-β2 , and ARF ) from 31 patients with primary lung tumors by quantitative fluorogenic real-time PCR. BAL from 10 age-matched noncancer patients
was used as a control.
Results: Promoter hypermethylation of at least one of the genes studied was detected in all 31 lung primary tumors; 27 (87%) CDH1 , 17 (55%) APC , 14 (45%) RASSF1A , 12 (39%) MGMT , 7 (23%) p16 , 3 (10%) GSTP1 , 3 (10%) RAR-β2 , and 0 (0%) ARF . Methylation was detected in CDH1 (48%), APC (29%), RASSF1A (29%), MGMT (58%), p16 (14%), GSTP1 (33%), RAR-β2 (0%), and ARF (0%) of BAL samples from matched methylation-positive primary tumors, and in every case, aberrant methylation in BAL DNA
was accompanied by methylation in the matched tumor samples. BAL samples from 10 controls without evidence of cancer revealed
no methylation of the MGMT , GSTP1 , p16 , ARF , or RAR-β2 genes whereas methylation of RASSF1 , CDH1 , and APC was detected at low levels. Overall, 21 (68%) of 31 BAL samples from cancer patients were positive for aberrant methylation.
Conclusion: Our findings suggest that promoter hypermethylation in BAL can be detected in the majority of lung cancer patients. This
approach needs to be evaluated in large early detection and surveillance studies of lung cancer.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>DOI: 10.1158/1078-0432.CCR-1111-3</identifier><identifier>PMID: 15073103</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Antineoplastic agents ; Biological and medical sciences ; Bronchoalveolar Lavage ; Bronchoalveolar Lavage Fluid ; Cell Line, Tumor ; CpG Islands ; DNA - chemistry ; DNA Methylation ; Gene Expression Regulation, Neoplastic ; Genes, Tumor Suppressor ; Humans ; Lung Neoplasms - genetics ; Lung Neoplasms - metabolism ; Medical sciences ; Middle Aged ; Pharmacology. Drug treatments ; Promoter Regions, Genetic ; Sulfites - pharmacology ; Time Factors ; Tumors</subject><ispartof>Clinical cancer research, 2004-04, Vol.10 (7), p.2284-2288</ispartof><rights>2004 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c412t-8603ddfc4455d782660230a83ffdf3615ce798f6d5f71fd56568407e04fa03973</citedby><cites>FETCH-LOGICAL-c412t-8603ddfc4455d782660230a83ffdf3615ce798f6d5f71fd56568407e04fa03973</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,3356,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15652595$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15073103$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>TOPALOGLU, Ozlem</creatorcontrib><creatorcontrib>HOQUE, Mohammad Obaidul</creatorcontrib><creatorcontrib>TOKUMARU, Yutaka</creatorcontrib><creatorcontrib>LEE, Juna</creatorcontrib><creatorcontrib>RATOVITSKI, Edward</creatorcontrib><creatorcontrib>SIDRANSKY, David</creatorcontrib><creatorcontrib>MOON, Chul-So</creatorcontrib><title>Detection of Promoter Hypermethylation of Multiple Genes in the Tumor and Bronchoalveolar Lavage of Patients with Lung Cancer</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>Purpose: Aberrant promoter hypermethylation of several known or putative tumor suppressor genes occurs frequently during the pathogenesis
of lung cancers and is a promising marker for cancer detection. We investigated the feasibility of detecting aberrant DNA
methylation in the bronchoalveolar lavage (BAL) samples of lung cancer patients.
Experimental Design: We examined the tumor and the matched BAL DNA for aberrant methylation of eight gene promoters ( CDH1 , APC , MGMT , RASSF1A , GSTP1 , p16 , RAR-β2 , and ARF ) from 31 patients with primary lung tumors by quantitative fluorogenic real-time PCR. BAL from 10 age-matched noncancer patients
was used as a control.
Results: Promoter hypermethylation of at least one of the genes studied was detected in all 31 lung primary tumors; 27 (87%) CDH1 , 17 (55%) APC , 14 (45%) RASSF1A , 12 (39%) MGMT , 7 (23%) p16 , 3 (10%) GSTP1 , 3 (10%) RAR-β2 , and 0 (0%) ARF . Methylation was detected in CDH1 (48%), APC (29%), RASSF1A (29%), MGMT (58%), p16 (14%), GSTP1 (33%), RAR-β2 (0%), and ARF (0%) of BAL samples from matched methylation-positive primary tumors, and in every case, aberrant methylation in BAL DNA
was accompanied by methylation in the matched tumor samples. BAL samples from 10 controls without evidence of cancer revealed
no methylation of the MGMT , GSTP1 , p16 , ARF , or RAR-β2 genes whereas methylation of RASSF1 , CDH1 , and APC was detected at low levels. Overall, 21 (68%) of 31 BAL samples from cancer patients were positive for aberrant methylation.
Conclusion: Our findings suggest that promoter hypermethylation in BAL can be detected in the majority of lung cancer patients. This
approach needs to be evaluated in large early detection and surveillance studies of lung cancer.</description><subject>Antineoplastic agents</subject><subject>Biological and medical sciences</subject><subject>Bronchoalveolar Lavage</subject><subject>Bronchoalveolar Lavage Fluid</subject><subject>Cell Line, Tumor</subject><subject>CpG Islands</subject><subject>DNA - chemistry</subject><subject>DNA Methylation</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Genes, Tumor Suppressor</subject><subject>Humans</subject><subject>Lung Neoplasms - genetics</subject><subject>Lung Neoplasms - metabolism</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Pharmacology. Drug treatments</subject><subject>Promoter Regions, Genetic</subject><subject>Sulfites - pharmacology</subject><subject>Time Factors</subject><subject>Tumors</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpNkM1u1DAUhS0Eon-8AULegNik9W-cWdIALdJUoKqsLeNcT4KceLCdVrPg3et0pgJvbMnfObr3Q-gtJeeUyuaCEtVURHB23ra3FS2n4i_QMZVSVZzV8mV5PyNH6CSl34RQQYl4jY6oJIpTwo_R38-QweYhTDg4_COGMWSI-Hq3hThC7nfePH_ezD4PWw_4CiZIeJhw7gHfzWOI2Ewdvoxhsn0w_h6CNxGvzb3ZwFNt6YApJ_ww5B6v52mDWzNZiGfolTM-wZvDfYp-fv1y115X6-9X39pP68oKynLV1IR3nbNCSNmphtU1YZyYhjvXOV5TaUGtGld30inqOlnLuhFEARHOEL5S_BR92PduY_gzQ8p6HJIF780EYU5a0abYYKyAYg_aGFKK4PQ2DqOJO02JXrTrxalenOqiXS_aNS-xd4f--dcI3b_QwXMB3h8Ak6zxLpb1h_QfV0smV7JwH_dcP2z6hyGCtk-iIiQw0fbLGEoz1gj-CLm0mWU</recordid><startdate>20040401</startdate><enddate>20040401</enddate><creator>TOPALOGLU, Ozlem</creator><creator>HOQUE, Mohammad Obaidul</creator><creator>TOKUMARU, Yutaka</creator><creator>LEE, Juna</creator><creator>RATOVITSKI, Edward</creator><creator>SIDRANSKY, David</creator><creator>MOON, Chul-So</creator><general>American Association for Cancer Research</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>7X8</scope></search><sort><creationdate>20040401</creationdate><title>Detection of Promoter Hypermethylation of Multiple Genes in the Tumor and Bronchoalveolar Lavage of Patients with Lung Cancer</title><author>TOPALOGLU, Ozlem ; HOQUE, Mohammad Obaidul ; TOKUMARU, Yutaka ; LEE, Juna ; RATOVITSKI, Edward ; SIDRANSKY, David ; MOON, Chul-So</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c412t-8603ddfc4455d782660230a83ffdf3615ce798f6d5f71fd56568407e04fa03973</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Antineoplastic agents</topic><topic>Biological and medical sciences</topic><topic>Bronchoalveolar Lavage</topic><topic>Bronchoalveolar Lavage Fluid</topic><topic>Cell Line, Tumor</topic><topic>CpG Islands</topic><topic>DNA - chemistry</topic><topic>DNA Methylation</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Genes, Tumor Suppressor</topic><topic>Humans</topic><topic>Lung Neoplasms - genetics</topic><topic>Lung Neoplasms - metabolism</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Pharmacology. Drug treatments</topic><topic>Promoter Regions, Genetic</topic><topic>Sulfites - pharmacology</topic><topic>Time Factors</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>TOPALOGLU, Ozlem</creatorcontrib><creatorcontrib>HOQUE, Mohammad Obaidul</creatorcontrib><creatorcontrib>TOKUMARU, Yutaka</creatorcontrib><creatorcontrib>LEE, Juna</creatorcontrib><creatorcontrib>RATOVITSKI, Edward</creatorcontrib><creatorcontrib>SIDRANSKY, David</creatorcontrib><creatorcontrib>MOON, Chul-So</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>MEDLINE - Academic</collection><jtitle>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>TOPALOGLU, Ozlem</au><au>HOQUE, Mohammad Obaidul</au><au>TOKUMARU, Yutaka</au><au>LEE, Juna</au><au>RATOVITSKI, Edward</au><au>SIDRANSKY, David</au><au>MOON, Chul-So</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Detection of Promoter Hypermethylation of Multiple Genes in the Tumor and Bronchoalveolar Lavage of Patients with Lung Cancer</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2004-04-01</date><risdate>2004</risdate><volume>10</volume><issue>7</issue><spage>2284</spage><epage>2288</epage><pages>2284-2288</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><abstract>Purpose: Aberrant promoter hypermethylation of several known or putative tumor suppressor genes occurs frequently during the pathogenesis
of lung cancers and is a promising marker for cancer detection. We investigated the feasibility of detecting aberrant DNA
methylation in the bronchoalveolar lavage (BAL) samples of lung cancer patients.
Experimental Design: We examined the tumor and the matched BAL DNA for aberrant methylation of eight gene promoters ( CDH1 , APC , MGMT , RASSF1A , GSTP1 , p16 , RAR-β2 , and ARF ) from 31 patients with primary lung tumors by quantitative fluorogenic real-time PCR. BAL from 10 age-matched noncancer patients
was used as a control.
Results: Promoter hypermethylation of at least one of the genes studied was detected in all 31 lung primary tumors; 27 (87%) CDH1 , 17 (55%) APC , 14 (45%) RASSF1A , 12 (39%) MGMT , 7 (23%) p16 , 3 (10%) GSTP1 , 3 (10%) RAR-β2 , and 0 (0%) ARF . Methylation was detected in CDH1 (48%), APC (29%), RASSF1A (29%), MGMT (58%), p16 (14%), GSTP1 (33%), RAR-β2 (0%), and ARF (0%) of BAL samples from matched methylation-positive primary tumors, and in every case, aberrant methylation in BAL DNA
was accompanied by methylation in the matched tumor samples. BAL samples from 10 controls without evidence of cancer revealed
no methylation of the MGMT , GSTP1 , p16 , ARF , or RAR-β2 genes whereas methylation of RASSF1 , CDH1 , and APC was detected at low levels. Overall, 21 (68%) of 31 BAL samples from cancer patients were positive for aberrant methylation.
Conclusion: Our findings suggest that promoter hypermethylation in BAL can be detected in the majority of lung cancer patients. This
approach needs to be evaluated in large early detection and surveillance studies of lung cancer.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>15073103</pmid><doi>10.1158/1078-0432.CCR-1111-3</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; American Association for Cancer Research; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Antineoplastic agents Biological and medical sciences Bronchoalveolar Lavage Bronchoalveolar Lavage Fluid Cell Line, Tumor CpG Islands DNA - chemistry DNA Methylation Gene Expression Regulation, Neoplastic Genes, Tumor Suppressor Humans Lung Neoplasms - genetics Lung Neoplasms - metabolism Medical sciences Middle Aged Pharmacology. Drug treatments Promoter Regions, Genetic Sulfites - pharmacology Time Factors Tumors |
| title | Detection of Promoter Hypermethylation of Multiple Genes in the Tumor and Bronchoalveolar Lavage of Patients with Lung Cancer |
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