DNA methylation profiles at precancerous stages associated with recurrence of lung adenocarcinoma
The aim of this study was to clarify the significance of DNA methylation alterations at precancerous stages of lung adenocarcinoma. Using single-CpG resolution Infinium array, genome-wide DNA methylation analysis was performed in 36 samples of normal lung tissue obtained from patients without any pr...
Gespeichert in:
| Veröffentlicht in: | PloS one 2013-03, Vol.8 (3), p.e59444 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | 3 |
| container_start_page | e59444 |
| container_title | PloS one |
| container_volume | 8 |
| creator | Sato, Takashi Arai, Eri Kohno, Takashi Tsuta, Koji Watanabe, Shun-ichi Soejima, Kenzo Betsuyaku, Tomoko Kanai, Yae |
| description | The aim of this study was to clarify the significance of DNA methylation alterations at precancerous stages of lung adenocarcinoma. Using single-CpG resolution Infinium array, genome-wide DNA methylation analysis was performed in 36 samples of normal lung tissue obtained from patients without any primary lung tumor, 145 samples of non-cancerous lung tissue (N) obtained from patients with lung adenocarcinomas, and 145 samples of tumorous tissue (T). Stepwise progression of DNA methylation alterations from normal lung tissue to non-cancerous lung tissue obtained from patients with lung adenocarcinomas, and then tumorous tissue samples, was observed at 3,270 CpG sites, suggesting that non-cancerous lung tissue obtained from patients with lung adenocarcinomas was at precancerous stages with DNA methylation alterations. At CpG sites of 2,083 genes, DNA methylation status in samples of non-cancerous lung tissue obtained from patients with lung adenocarcinomas was significantly correlated with recurrence after establishment of lung adenocarcinomas. Among such recurrence-related genes, 28 genes are normally unmethylated (average β-values based on Infinium assay in normal lung tissue samples was less than 0.2) and their DNA hypermethylation at precancerous stages was strengthened during progression to lung adenocarcinomas (Δβ(T-N)>0.1). Among these 28 genes, we focused on 6 for which implications in transcription regulation, apoptosis or cell adhesion had been reported. DNA hypermethylation of the ADCY5, EVX1, GFRA1, PDE9A, and TBX20 genes resulted in reduced mRNA expression in tumorous tissue samples. 5-Aza-2'-deoxycytidine treatment of lung cancer cell lines restored the mRNA expression levels of these 5 genes. Reduced mRNA expression in tumorous tissue samples was significantly correlated with tumor aggressiveness. These data suggest that DNA methylation alterations at precancerous stages determine tumor aggressiveness and outcome through silencing of specific genes. |
| doi_str_mv | 10.1371/journal.pone.0059444 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_plos_</sourceid><recordid>TN_cdi_plos_journals_1330900399</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><doaj_id>oai_doaj_org_article_b333a7cb620840e5a2048b43710eb6a3</doaj_id><sourcerecordid>2949868581</sourcerecordid><originalsourceid>FETCH-LOGICAL-c526t-49e2766bbe2d32af9e99ebdf06f02198a8aeddfecaab0e670260517a1a93b5743</originalsourceid><addsrcrecordid>eNp1UstuFDEQHCEQCYE_QGCJ8y5-jWd8QYrCK1IEFzhbbU_Prlez9mJ7QPl7vOwkSg6c3Oquri6Vq2leM7pmomPvd3FOAab1IQZcU9pqKeWT5pxpwVeKU_H0QX3WvMh5V0GiV-p5c8ZFKyVV_XkDH79dkj2W7e0ExcdADimOfsJMoNQaHQSHKc6Z5AKbYzvn6DwUHMgfX7akQuaUsKJIHMk0hw2BAUN0kJwPcQ8vm2cjTBlfLe9F8_Pzpx9XX1c3379cX13erFzLVVlJjbxTylrkg-AwatQa7TBSNVLOdA894DCMVRBYiqqjXNGWdcBAC9t2Ulw0b0-8hylms7iTDROCakqF1hVxfUIMEXbmkPwe0q2J4M2_RkwbA6l4N6GxQgjonK3m9ZJiC5zK3srqO0WrQFSuD8u12e5xcBhKgukR6eNJ8Fuzib-NUFT34kjwbiFI8deMufxHsjyhXIo5JxzvLzBqjjG42zLHGJglBnXtzUN190t3_y7-AnTksvM</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1330900399</pqid></control><display><type>article</type><title>DNA methylation profiles at precancerous stages associated with recurrence of lung adenocarcinoma</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Public Library of Science (PLoS) Journals Open Access</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Sato, Takashi ; Arai, Eri ; Kohno, Takashi ; Tsuta, Koji ; Watanabe, Shun-ichi ; Soejima, Kenzo ; Betsuyaku, Tomoko ; Kanai, Yae</creator><contributor>Futscher, Bernard W.</contributor><creatorcontrib>Sato, Takashi ; Arai, Eri ; Kohno, Takashi ; Tsuta, Koji ; Watanabe, Shun-ichi ; Soejima, Kenzo ; Betsuyaku, Tomoko ; Kanai, Yae ; Futscher, Bernard W.</creatorcontrib><description>The aim of this study was to clarify the significance of DNA methylation alterations at precancerous stages of lung adenocarcinoma. Using single-CpG resolution Infinium array, genome-wide DNA methylation analysis was performed in 36 samples of normal lung tissue obtained from patients without any primary lung tumor, 145 samples of non-cancerous lung tissue (N) obtained from patients with lung adenocarcinomas, and 145 samples of tumorous tissue (T). Stepwise progression of DNA methylation alterations from normal lung tissue to non-cancerous lung tissue obtained from patients with lung adenocarcinomas, and then tumorous tissue samples, was observed at 3,270 CpG sites, suggesting that non-cancerous lung tissue obtained from patients with lung adenocarcinomas was at precancerous stages with DNA methylation alterations. At CpG sites of 2,083 genes, DNA methylation status in samples of non-cancerous lung tissue obtained from patients with lung adenocarcinomas was significantly correlated with recurrence after establishment of lung adenocarcinomas. Among such recurrence-related genes, 28 genes are normally unmethylated (average β-values based on Infinium assay in normal lung tissue samples was less than 0.2) and their DNA hypermethylation at precancerous stages was strengthened during progression to lung adenocarcinomas (Δβ(T-N)>0.1). Among these 28 genes, we focused on 6 for which implications in transcription regulation, apoptosis or cell adhesion had been reported. DNA hypermethylation of the ADCY5, EVX1, GFRA1, PDE9A, and TBX20 genes resulted in reduced mRNA expression in tumorous tissue samples. 5-Aza-2'-deoxycytidine treatment of lung cancer cell lines restored the mRNA expression levels of these 5 genes. Reduced mRNA expression in tumorous tissue samples was significantly correlated with tumor aggressiveness. These data suggest that DNA methylation alterations at precancerous stages determine tumor aggressiveness and outcome through silencing of specific genes.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0059444</identifier><identifier>PMID: 23544068</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adenocarcinoma ; Adenocarcinoma - genetics ; Adenocarcinoma - pathology ; Adenocarcinoma of Lung ; Adult ; Aged ; Aged, 80 and over ; Apoptosis ; Azacitidine - pharmacology ; Biology ; Cell adhesion ; CpG islands ; Deoxyribonucleic acid ; DNA ; DNA methylation ; DNA Methylation - drug effects ; DNA Methylation - genetics ; DNA Probes - metabolism ; Epigenetics ; Female ; Gene expression ; Gene Expression Regulation, Neoplastic - drug effects ; Gene regulation ; Gene Silencing ; Genes ; Genes, Neoplasm - genetics ; Genomes ; Humans ; Leukemia ; Lung cancer ; Lung diseases ; Lung Neoplasms - genetics ; Lung Neoplasms - pathology ; Male ; Medical imaging ; Medicine ; Middle Aged ; Mutation ; Neoplasm Recurrence, Local - genetics ; Neoplasm Recurrence, Local - pathology ; Neoplasm Staging ; Pathology ; Patients ; Precancerous Conditions - genetics ; Precancerous Conditions - pathology ; Proportional Hazards Models ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Thoracic surgery ; Transcription ; Tumor cell lines ; Tumors</subject><ispartof>PloS one, 2013-03, Vol.8 (3), p.e59444</ispartof><rights>2013 Sato et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2013 Sato et al 2013 Sato et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-49e2766bbe2d32af9e99ebdf06f02198a8aeddfecaab0e670260517a1a93b5743</citedby><cites>FETCH-LOGICAL-c526t-49e2766bbe2d32af9e99ebdf06f02198a8aeddfecaab0e670260517a1a93b5743</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3609833/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3609833/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23544068$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Futscher, Bernard W.</contributor><creatorcontrib>Sato, Takashi</creatorcontrib><creatorcontrib>Arai, Eri</creatorcontrib><creatorcontrib>Kohno, Takashi</creatorcontrib><creatorcontrib>Tsuta, Koji</creatorcontrib><creatorcontrib>Watanabe, Shun-ichi</creatorcontrib><creatorcontrib>Soejima, Kenzo</creatorcontrib><creatorcontrib>Betsuyaku, Tomoko</creatorcontrib><creatorcontrib>Kanai, Yae</creatorcontrib><title>DNA methylation profiles at precancerous stages associated with recurrence of lung adenocarcinoma</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The aim of this study was to clarify the significance of DNA methylation alterations at precancerous stages of lung adenocarcinoma. Using single-CpG resolution Infinium array, genome-wide DNA methylation analysis was performed in 36 samples of normal lung tissue obtained from patients without any primary lung tumor, 145 samples of non-cancerous lung tissue (N) obtained from patients with lung adenocarcinomas, and 145 samples of tumorous tissue (T). Stepwise progression of DNA methylation alterations from normal lung tissue to non-cancerous lung tissue obtained from patients with lung adenocarcinomas, and then tumorous tissue samples, was observed at 3,270 CpG sites, suggesting that non-cancerous lung tissue obtained from patients with lung adenocarcinomas was at precancerous stages with DNA methylation alterations. At CpG sites of 2,083 genes, DNA methylation status in samples of non-cancerous lung tissue obtained from patients with lung adenocarcinomas was significantly correlated with recurrence after establishment of lung adenocarcinomas. Among such recurrence-related genes, 28 genes are normally unmethylated (average β-values based on Infinium assay in normal lung tissue samples was less than 0.2) and their DNA hypermethylation at precancerous stages was strengthened during progression to lung adenocarcinomas (Δβ(T-N)>0.1). Among these 28 genes, we focused on 6 for which implications in transcription regulation, apoptosis or cell adhesion had been reported. DNA hypermethylation of the ADCY5, EVX1, GFRA1, PDE9A, and TBX20 genes resulted in reduced mRNA expression in tumorous tissue samples. 5-Aza-2'-deoxycytidine treatment of lung cancer cell lines restored the mRNA expression levels of these 5 genes. Reduced mRNA expression in tumorous tissue samples was significantly correlated with tumor aggressiveness. These data suggest that DNA methylation alterations at precancerous stages determine tumor aggressiveness and outcome through silencing of specific genes.</description><subject>Adenocarcinoma</subject><subject>Adenocarcinoma - genetics</subject><subject>Adenocarcinoma - pathology</subject><subject>Adenocarcinoma of Lung</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Apoptosis</subject><subject>Azacitidine - pharmacology</subject><subject>Biology</subject><subject>Cell adhesion</subject><subject>CpG islands</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA methylation</subject><subject>DNA Methylation - drug effects</subject><subject>DNA Methylation - genetics</subject><subject>DNA Probes - metabolism</subject><subject>Epigenetics</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Neoplastic - drug effects</subject><subject>Gene regulation</subject><subject>Gene Silencing</subject><subject>Genes</subject><subject>Genes, Neoplasm - genetics</subject><subject>Genomes</subject><subject>Humans</subject><subject>Leukemia</subject><subject>Lung cancer</subject><subject>Lung diseases</subject><subject>Lung Neoplasms - genetics</subject><subject>Lung Neoplasms - pathology</subject><subject>Male</subject><subject>Medical imaging</subject><subject>Medicine</subject><subject>Middle Aged</subject><subject>Mutation</subject><subject>Neoplasm Recurrence, Local - genetics</subject><subject>Neoplasm Recurrence, Local - pathology</subject><subject>Neoplasm Staging</subject><subject>Pathology</subject><subject>Patients</subject><subject>Precancerous Conditions - genetics</subject><subject>Precancerous Conditions - pathology</subject><subject>Proportional Hazards Models</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Thoracic surgery</subject><subject>Transcription</subject><subject>Tumor cell lines</subject><subject>Tumors</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNp1UstuFDEQHCEQCYE_QGCJ8y5-jWd8QYrCK1IEFzhbbU_Prlez9mJ7QPl7vOwkSg6c3Oquri6Vq2leM7pmomPvd3FOAab1IQZcU9pqKeWT5pxpwVeKU_H0QX3WvMh5V0GiV-p5c8ZFKyVV_XkDH79dkj2W7e0ExcdADimOfsJMoNQaHQSHKc6Z5AKbYzvn6DwUHMgfX7akQuaUsKJIHMk0hw2BAUN0kJwPcQ8vm2cjTBlfLe9F8_Pzpx9XX1c3379cX13erFzLVVlJjbxTylrkg-AwatQa7TBSNVLOdA894DCMVRBYiqqjXNGWdcBAC9t2Ulw0b0-8hylms7iTDROCakqF1hVxfUIMEXbmkPwe0q2J4M2_RkwbA6l4N6GxQgjonK3m9ZJiC5zK3srqO0WrQFSuD8u12e5xcBhKgukR6eNJ8Fuzib-NUFT34kjwbiFI8deMufxHsjyhXIo5JxzvLzBqjjG42zLHGJglBnXtzUN190t3_y7-AnTksvM</recordid><startdate>20130327</startdate><enddate>20130327</enddate><creator>Sato, Takashi</creator><creator>Arai, Eri</creator><creator>Kohno, Takashi</creator><creator>Tsuta, Koji</creator><creator>Watanabe, Shun-ichi</creator><creator>Soejima, Kenzo</creator><creator>Betsuyaku, Tomoko</creator><creator>Kanai, Yae</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><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>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20130327</creationdate><title>DNA methylation profiles at precancerous stages associated with recurrence of lung adenocarcinoma</title><author>Sato, Takashi ; Arai, Eri ; Kohno, Takashi ; Tsuta, Koji ; Watanabe, Shun-ichi ; Soejima, Kenzo ; Betsuyaku, Tomoko ; Kanai, Yae</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c526t-49e2766bbe2d32af9e99ebdf06f02198a8aeddfecaab0e670260517a1a93b5743</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adenocarcinoma</topic><topic>Adenocarcinoma - genetics</topic><topic>Adenocarcinoma - pathology</topic><topic>Adenocarcinoma of Lung</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Apoptosis</topic><topic>Azacitidine - pharmacology</topic><topic>Biology</topic><topic>Cell adhesion</topic><topic>CpG islands</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA methylation</topic><topic>DNA Methylation - drug effects</topic><topic>DNA Methylation - genetics</topic><topic>DNA Probes - metabolism</topic><topic>Epigenetics</topic><topic>Female</topic><topic>Gene expression</topic><topic>Gene Expression Regulation, Neoplastic - drug effects</topic><topic>Gene regulation</topic><topic>Gene Silencing</topic><topic>Genes</topic><topic>Genes, Neoplasm - genetics</topic><topic>Genomes</topic><topic>Humans</topic><topic>Leukemia</topic><topic>Lung cancer</topic><topic>Lung diseases</topic><topic>Lung Neoplasms - genetics</topic><topic>Lung Neoplasms - pathology</topic><topic>Male</topic><topic>Medical imaging</topic><topic>Medicine</topic><topic>Middle Aged</topic><topic>Mutation</topic><topic>Neoplasm Recurrence, Local - genetics</topic><topic>Neoplasm Recurrence, Local - pathology</topic><topic>Neoplasm Staging</topic><topic>Pathology</topic><topic>Patients</topic><topic>Precancerous Conditions - genetics</topic><topic>Precancerous Conditions - pathology</topic><topic>Proportional Hazards Models</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Thoracic surgery</topic><topic>Transcription</topic><topic>Tumor cell lines</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sato, Takashi</creatorcontrib><creatorcontrib>Arai, Eri</creatorcontrib><creatorcontrib>Kohno, Takashi</creatorcontrib><creatorcontrib>Tsuta, Koji</creatorcontrib><creatorcontrib>Watanabe, Shun-ichi</creatorcontrib><creatorcontrib>Soejima, Kenzo</creatorcontrib><creatorcontrib>Betsuyaku, Tomoko</creatorcontrib><creatorcontrib>Kanai, Yae</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Access via ProQuest (Open Access)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sato, Takashi</au><au>Arai, Eri</au><au>Kohno, Takashi</au><au>Tsuta, Koji</au><au>Watanabe, Shun-ichi</au><au>Soejima, Kenzo</au><au>Betsuyaku, Tomoko</au><au>Kanai, Yae</au><au>Futscher, Bernard W.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>DNA methylation profiles at precancerous stages associated with recurrence of lung adenocarcinoma</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-03-27</date><risdate>2013</risdate><volume>8</volume><issue>3</issue><spage>e59444</spage><pages>e59444-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>The aim of this study was to clarify the significance of DNA methylation alterations at precancerous stages of lung adenocarcinoma. Using single-CpG resolution Infinium array, genome-wide DNA methylation analysis was performed in 36 samples of normal lung tissue obtained from patients without any primary lung tumor, 145 samples of non-cancerous lung tissue (N) obtained from patients with lung adenocarcinomas, and 145 samples of tumorous tissue (T). Stepwise progression of DNA methylation alterations from normal lung tissue to non-cancerous lung tissue obtained from patients with lung adenocarcinomas, and then tumorous tissue samples, was observed at 3,270 CpG sites, suggesting that non-cancerous lung tissue obtained from patients with lung adenocarcinomas was at precancerous stages with DNA methylation alterations. At CpG sites of 2,083 genes, DNA methylation status in samples of non-cancerous lung tissue obtained from patients with lung adenocarcinomas was significantly correlated with recurrence after establishment of lung adenocarcinomas. Among such recurrence-related genes, 28 genes are normally unmethylated (average β-values based on Infinium assay in normal lung tissue samples was less than 0.2) and their DNA hypermethylation at precancerous stages was strengthened during progression to lung adenocarcinomas (Δβ(T-N)>0.1). Among these 28 genes, we focused on 6 for which implications in transcription regulation, apoptosis or cell adhesion had been reported. DNA hypermethylation of the ADCY5, EVX1, GFRA1, PDE9A, and TBX20 genes resulted in reduced mRNA expression in tumorous tissue samples. 5-Aza-2'-deoxycytidine treatment of lung cancer cell lines restored the mRNA expression levels of these 5 genes. Reduced mRNA expression in tumorous tissue samples was significantly correlated with tumor aggressiveness. These data suggest that DNA methylation alterations at precancerous stages determine tumor aggressiveness and outcome through silencing of specific genes.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23544068</pmid><doi>10.1371/journal.pone.0059444</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2013-03, Vol.8 (3), p.e59444 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1330900399 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adenocarcinoma Adenocarcinoma - genetics Adenocarcinoma - pathology Adenocarcinoma of Lung Adult Aged Aged, 80 and over Apoptosis Azacitidine - pharmacology Biology Cell adhesion CpG islands Deoxyribonucleic acid DNA DNA methylation DNA Methylation - drug effects DNA Methylation - genetics DNA Probes - metabolism Epigenetics Female Gene expression Gene Expression Regulation, Neoplastic - drug effects Gene regulation Gene Silencing Genes Genes, Neoplasm - genetics Genomes Humans Leukemia Lung cancer Lung diseases Lung Neoplasms - genetics Lung Neoplasms - pathology Male Medical imaging Medicine Middle Aged Mutation Neoplasm Recurrence, Local - genetics Neoplasm Recurrence, Local - pathology Neoplasm Staging Pathology Patients Precancerous Conditions - genetics Precancerous Conditions - pathology Proportional Hazards Models RNA, Messenger - genetics RNA, Messenger - metabolism Thoracic surgery Transcription Tumor cell lines Tumors |
| title | DNA methylation profiles at precancerous stages associated with recurrence of lung adenocarcinoma |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-23T19%3A27%3A44IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=DNA%20methylation%20profiles%20at%20precancerous%20stages%20associated%20with%20recurrence%20of%20lung%20adenocarcinoma&rft.jtitle=PloS%20one&rft.au=Sato,%20Takashi&rft.date=2013-03-27&rft.volume=8&rft.issue=3&rft.spage=e59444&rft.pages=e59444-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0059444&rft_dat=%3Cproquest_plos_%3E2949868581%3C/proquest_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1330900399&rft_id=info:pmid/23544068&rft_doaj_id=oai_doaj_org_article_b333a7cb620840e5a2048b43710eb6a3&rfr_iscdi=true |