Transcriptome analysis of microdissected pancreatic intraepithelial neoplastic lesions
Pancreatic ductal adenocarcinoma (PDAC) carries the most dismal prognosis of all solid tumours. Both the late clinical presentation of patients, due to lack of early symptoms, as well as the rapid and aggressive course of the disease contribute to the extremely high mortality of this malignancy. Rec...
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| Veröffentlicht in: | Oncogene 2005-10, Vol.24 (44), p.6626-6636 |
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| creator | Buchholz, Malte Braun, Mike Heidenblut, Anna Kestler, Hans A Klöppel, Günter Schmiegel, Wolff Hahn, Stephan A Lüttges, Jutta Gress, Thomas M |
| description | Pancreatic ductal adenocarcinoma (PDAC) carries the most dismal prognosis of all solid tumours. Both the late clinical presentation of patients, due to lack of early symptoms, as well as the rapid and aggressive course of the disease contribute to the extremely high mortality of this malignancy. Recently, a multistep progression model for PDAC integrating morphological, clinical and molecular evidence has been proposed. Putative precursor lesions, termed pancreatic intraepithelial neoplasia (PanIN), are classified into three different grades (PanIN-1 through -3) based on the degree of cellular atypia they display. We have conducted large-scale expression profiling analyses of microdissected cells from normal pancreatic ducts, PanINs of different grades and PDACs using whole-genome oligonucleotide microarrays. Verification of hybridisation results for selected genes was performed using quantitative real-time PCR and immunohistochemical analyses on PanIN tissue microarrays. Comparison of the expression profiles demonstrated that the greatest changes in gene expression occur between PanIN stages 1B and 2, suggesting that PanIN-2 may represent the first truly preneoplastic stage in PDAC progression. Our results identify a large number of potential target genes for the development of novel molecular diagnostic and therapeutic tools for the prevention and early diagnosis of PDAC and provide novel insights into the pathophysiological mechanisms involved in tumour progression in the pancreas. |
| doi_str_mv | 10.1038/sj.onc.1208804 |
| format | Article |
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Both the late clinical presentation of patients, due to lack of early symptoms, as well as the rapid and aggressive course of the disease contribute to the extremely high mortality of this malignancy. Recently, a multistep progression model for PDAC integrating morphological, clinical and molecular evidence has been proposed. Putative precursor lesions, termed pancreatic intraepithelial neoplasia (PanIN), are classified into three different grades (PanIN-1 through -3) based on the degree of cellular atypia they display. We have conducted large-scale expression profiling analyses of microdissected cells from normal pancreatic ducts, PanINs of different grades and PDACs using whole-genome oligonucleotide microarrays. Verification of hybridisation results for selected genes was performed using quantitative real-time PCR and immunohistochemical analyses on PanIN tissue microarrays. Comparison of the expression profiles demonstrated that the greatest changes in gene expression occur between PanIN stages 1B and 2, suggesting that PanIN-2 may represent the first truly preneoplastic stage in PDAC progression. Our results identify a large number of potential target genes for the development of novel molecular diagnostic and therapeutic tools for the prevention and early diagnosis of PDAC and provide novel insights into the pathophysiological mechanisms involved in tumour progression in the pancreas.</description><identifier>ISSN: 0950-9232</identifier><identifier>EISSN: 1476-5594</identifier><identifier>DOI: 10.1038/sj.onc.1208804</identifier><identifier>PMID: 16103885</identifier><identifier>CODEN: ONCNES</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Adenocarcinoma ; Apoptosis ; Base Sequence ; Biological and medical sciences ; Carcinoma in Situ - genetics ; Cell Biology ; Cell physiology ; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes ; Cluster Analysis ; DNA microarrays ; DNA Primers ; Fundamental and applied biological sciences. Psychology ; Gene expression ; Gene Expression Profiling ; Genomes ; Human Genetics ; Humans ; Hybridization ; Immunohistochemistry ; Internal Medicine ; Malignancy ; Medical prognosis ; Medicine ; Medicine & Public Health ; Molecular and cellular biology ; Morphology ; Mortality ; Oligonucleotide Array Sequence Analysis ; Oligonucleotides ; Oncology ; original-paper ; Pancreas ; Pancreatic cancer ; Pancreatic Neoplasms - genetics ; Pathology ; RNA, Messenger - genetics ; Solid tumors ; Surgery ; Transcriptomes</subject><ispartof>Oncogene, 2005-10, Vol.24 (44), p.6626-6636</ispartof><rights>Springer Nature Limited 2005</rights><rights>2005 INIST-CNRS</rights><rights>COPYRIGHT 2005 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Oct 6, 2005</rights><rights>Nature Publishing Group 2005.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c644t-5cf5c79be0134e2c236955d2144d0dfdfe04a473a3b02c4dfcc0c64116ebed3c3</citedby><cites>FETCH-LOGICAL-c644t-5cf5c79be0134e2c236955d2144d0dfdfe04a473a3b02c4dfcc0c64116ebed3c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/sj.onc.1208804$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/sj.onc.1208804$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,2727,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17173607$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16103885$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Buchholz, Malte</creatorcontrib><creatorcontrib>Braun, Mike</creatorcontrib><creatorcontrib>Heidenblut, Anna</creatorcontrib><creatorcontrib>Kestler, Hans A</creatorcontrib><creatorcontrib>Klöppel, Günter</creatorcontrib><creatorcontrib>Schmiegel, Wolff</creatorcontrib><creatorcontrib>Hahn, Stephan A</creatorcontrib><creatorcontrib>Lüttges, Jutta</creatorcontrib><creatorcontrib>Gress, Thomas M</creatorcontrib><creatorcontrib>for the German Pancreatic Cancer Net of the Deutsche Krebshilfe</creatorcontrib><title>Transcriptome analysis of microdissected pancreatic intraepithelial neoplastic lesions</title><title>Oncogene</title><addtitle>Oncogene</addtitle><addtitle>Oncogene</addtitle><description>Pancreatic ductal adenocarcinoma (PDAC) carries the most dismal prognosis of all solid tumours. Both the late clinical presentation of patients, due to lack of early symptoms, as well as the rapid and aggressive course of the disease contribute to the extremely high mortality of this malignancy. Recently, a multistep progression model for PDAC integrating morphological, clinical and molecular evidence has been proposed. Putative precursor lesions, termed pancreatic intraepithelial neoplasia (PanIN), are classified into three different grades (PanIN-1 through -3) based on the degree of cellular atypia they display. We have conducted large-scale expression profiling analyses of microdissected cells from normal pancreatic ducts, PanINs of different grades and PDACs using whole-genome oligonucleotide microarrays. Verification of hybridisation results for selected genes was performed using quantitative real-time PCR and immunohistochemical analyses on PanIN tissue microarrays. Comparison of the expression profiles demonstrated that the greatest changes in gene expression occur between PanIN stages 1B and 2, suggesting that PanIN-2 may represent the first truly preneoplastic stage in PDAC progression. Our results identify a large number of potential target genes for the development of novel molecular diagnostic and therapeutic tools for the prevention and early diagnosis of PDAC and provide novel insights into the pathophysiological mechanisms involved in tumour progression in the pancreas.</description><subject>Adenocarcinoma</subject><subject>Apoptosis</subject><subject>Base Sequence</subject><subject>Biological and medical sciences</subject><subject>Carcinoma in Situ - genetics</subject><subject>Cell Biology</subject><subject>Cell physiology</subject><subject>Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes</subject><subject>Cluster Analysis</subject><subject>DNA microarrays</subject><subject>DNA Primers</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>Genomes</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Hybridization</subject><subject>Immunohistochemistry</subject><subject>Internal Medicine</subject><subject>Malignancy</subject><subject>Medical prognosis</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Molecular and cellular biology</subject><subject>Morphology</subject><subject>Mortality</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Oligonucleotides</subject><subject>Oncology</subject><subject>original-paper</subject><subject>Pancreas</subject><subject>Pancreatic cancer</subject><subject>Pancreatic Neoplasms - genetics</subject><subject>Pathology</subject><subject>RNA, Messenger - genetics</subject><subject>Solid tumors</subject><subject>Surgery</subject><subject>Transcriptomes</subject><issn>0950-9232</issn><issn>1476-5594</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqFkk1v1DAQhiMEotvClRsoAsEtW387OVYVBaRKXApXy2tPileOEzzJof8erzbSItQK-WDJ87wz45m3qt5QsqWEt5e4347JbSkjbUvEs2pDhVaNlJ14Xm1IJ0nTMc7OqnPEPSFEd4S9rM6oOohbual-3mWb0OUwzeMAtU02PmDAeuzrIbg8-oAIbgZfTza5DHYOrg5pzhamMP-CGGysE4xTtHgIRcAwJnxVvehtRHi93hfVj5vPd9dfm9vvX75dX902TgkxN9L10uluB4RyAcwxrjopPaNCeOJ73wMRVmhu-Y4wJ3zvHClKShXswHPHL6pPx7xTHn8vgLMZAjqI0ZaeFjSqVUoLLv4L0k5zxgQp4Id_wP245DIWNKxU5lKqjhfq_ZMU01woLf9KdW8jmJD6sYzNHeqaK9p2RIlW00JtH6HK8VA2MCboQ3l_TFDWg5ihN1MOg80PhhJz2KvBvSmmMKspiuDd2uyyG8Cf8NUFBfi4AhadjX2xhAt44jTVXBFduMsjhyWU7iGffv1k6bdHRbLzkuGUco3_ASHG2Kg</recordid><startdate>20051006</startdate><enddate>20051006</enddate><creator>Buchholz, Malte</creator><creator>Braun, Mike</creator><creator>Heidenblut, Anna</creator><creator>Kestler, Hans A</creator><creator>Klöppel, Günter</creator><creator>Schmiegel, Wolff</creator><creator>Hahn, Stephan A</creator><creator>Lüttges, Jutta</creator><creator>Gress, Thomas M</creator><general>Nature Publishing Group UK</general><general>Nature Publishing</general><general>Nature Publishing Group</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>3V.</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20051006</creationdate><title>Transcriptome analysis of microdissected pancreatic intraepithelial neoplastic lesions</title><author>Buchholz, Malte ; Braun, Mike ; Heidenblut, Anna ; Kestler, Hans A ; Klöppel, Günter ; Schmiegel, Wolff ; Hahn, Stephan A ; Lüttges, Jutta ; Gress, Thomas M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c644t-5cf5c79be0134e2c236955d2144d0dfdfe04a473a3b02c4dfcc0c64116ebed3c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Adenocarcinoma</topic><topic>Apoptosis</topic><topic>Base Sequence</topic><topic>Biological and medical sciences</topic><topic>Carcinoma in Situ - genetics</topic><topic>Cell Biology</topic><topic>Cell physiology</topic><topic>Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes</topic><topic>Cluster Analysis</topic><topic>DNA microarrays</topic><topic>DNA Primers</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene expression</topic><topic>Gene Expression Profiling</topic><topic>Genomes</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>Hybridization</topic><topic>Immunohistochemistry</topic><topic>Internal Medicine</topic><topic>Malignancy</topic><topic>Medical prognosis</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Molecular and cellular biology</topic><topic>Morphology</topic><topic>Mortality</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>Oligonucleotides</topic><topic>Oncology</topic><topic>original-paper</topic><topic>Pancreas</topic><topic>Pancreatic cancer</topic><topic>Pancreatic Neoplasms - genetics</topic><topic>Pathology</topic><topic>RNA, Messenger - genetics</topic><topic>Solid tumors</topic><topic>Surgery</topic><topic>Transcriptomes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Buchholz, Malte</creatorcontrib><creatorcontrib>Braun, Mike</creatorcontrib><creatorcontrib>Heidenblut, Anna</creatorcontrib><creatorcontrib>Kestler, Hans A</creatorcontrib><creatorcontrib>Klöppel, Günter</creatorcontrib><creatorcontrib>Schmiegel, Wolff</creatorcontrib><creatorcontrib>Hahn, Stephan A</creatorcontrib><creatorcontrib>Lüttges, Jutta</creatorcontrib><creatorcontrib>Gress, Thomas M</creatorcontrib><creatorcontrib>for the German Pancreatic Cancer Net of the Deutsche Krebshilfe</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>ProQuest Central (Corporate)</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</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 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>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</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>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</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>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Oncogene</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Buchholz, Malte</au><au>Braun, Mike</au><au>Heidenblut, Anna</au><au>Kestler, Hans A</au><au>Klöppel, Günter</au><au>Schmiegel, Wolff</au><au>Hahn, Stephan A</au><au>Lüttges, Jutta</au><au>Gress, Thomas M</au><aucorp>for the German Pancreatic Cancer Net of the Deutsche Krebshilfe</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Transcriptome analysis of microdissected pancreatic intraepithelial neoplastic lesions</atitle><jtitle>Oncogene</jtitle><stitle>Oncogene</stitle><addtitle>Oncogene</addtitle><date>2005-10-06</date><risdate>2005</risdate><volume>24</volume><issue>44</issue><spage>6626</spage><epage>6636</epage><pages>6626-6636</pages><issn>0950-9232</issn><eissn>1476-5594</eissn><coden>ONCNES</coden><abstract>Pancreatic ductal adenocarcinoma (PDAC) carries the most dismal prognosis of all solid tumours. Both the late clinical presentation of patients, due to lack of early symptoms, as well as the rapid and aggressive course of the disease contribute to the extremely high mortality of this malignancy. Recently, a multistep progression model for PDAC integrating morphological, clinical and molecular evidence has been proposed. Putative precursor lesions, termed pancreatic intraepithelial neoplasia (PanIN), are classified into three different grades (PanIN-1 through -3) based on the degree of cellular atypia they display. We have conducted large-scale expression profiling analyses of microdissected cells from normal pancreatic ducts, PanINs of different grades and PDACs using whole-genome oligonucleotide microarrays. Verification of hybridisation results for selected genes was performed using quantitative real-time PCR and immunohistochemical analyses on PanIN tissue microarrays. Comparison of the expression profiles demonstrated that the greatest changes in gene expression occur between PanIN stages 1B and 2, suggesting that PanIN-2 may represent the first truly preneoplastic stage in PDAC progression. Our results identify a large number of potential target genes for the development of novel molecular diagnostic and therapeutic tools for the prevention and early diagnosis of PDAC and provide novel insights into the pathophysiological mechanisms involved in tumour progression in the pancreas.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>16103885</pmid><doi>10.1038/sj.onc.1208804</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adenocarcinoma Apoptosis Base Sequence Biological and medical sciences Carcinoma in Situ - genetics Cell Biology Cell physiology Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes Cluster Analysis DNA microarrays DNA Primers Fundamental and applied biological sciences. Psychology Gene expression Gene Expression Profiling Genomes Human Genetics Humans Hybridization Immunohistochemistry Internal Medicine Malignancy Medical prognosis Medicine Medicine & Public Health Molecular and cellular biology Morphology Mortality Oligonucleotide Array Sequence Analysis Oligonucleotides Oncology original-paper Pancreas Pancreatic cancer Pancreatic Neoplasms - genetics Pathology RNA, Messenger - genetics Solid tumors Surgery Transcriptomes |
| title | Transcriptome analysis of microdissected pancreatic intraepithelial neoplastic lesions |
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