High-Resolution Characterization of the Pancreatic Adenocarcinoma Genome
The pancreatic adenocarcinoma genome harbors multiple amplifications and deletions, pointing to the existence of numerous oncogenes and tumor suppressor genes driving the genesis and progression of this lethal cancer. Here, array comparative genomic hybridization on a cDNA microarray platform and in...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2004-06, Vol.101 (24), p.9067-9072 |
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| creator | Aguirre, Andrew J. Brennan, Cameron Bailey, Gerald Sinha, Raktim Feng, Bin Leo, Christopher Zhang, Yunyu Zhang, Jean Gans, Joseph D. Bardeesy, Nabeel Cauwels, Craig Cordon-Cardo, Carlos Redston, Mark S. DePinho, Ronald A. Chin, Lynda Cantley, Lewis C. |
| description | The pancreatic adenocarcinoma genome harbors multiple amplifications and deletions, pointing to the existence of numerous oncogenes and tumor suppressor genes driving the genesis and progression of this lethal cancer. Here, array comparative genomic hybridization on a cDNA microarray platform and informatics tools have been used to define the copy number alterations in a panel of 24 pancreatic adenocarcinoma cell lines and 13 primary tumor specimens. This high-resolution genomic analysis has identified all known regional gains and losses as well as many previously uncharacterized highly recurrent copy number alterations. A systematic prioritization scheme has selected 64 focal minimal common regions (MCRs) of recurrent copy number change. These MCRs possess a median size of 2.7 megabases (Mb), with 21 (33%) MCRs spanning 1 Mb or less (median of 0.33 Mb) and possessing an average of 15 annotated genes. Furthermore, complementary expression profile analysis of a significant fraction of the genes residing within these 64 prioritized MCRs has enabled the identification of a subset of candidates with statistically significant association between gene dosage and mRNA expression. Thus, the integration of DNA and RNA profiles provides a highly productive entry point for the discovery of genes involved in the pathogenesis of pancreatic adenocarcinoma. |
| doi_str_mv | 10.1073/pnas.0402932101 |
| format | Article |
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Here, array comparative genomic hybridization on a cDNA microarray platform and informatics tools have been used to define the copy number alterations in a panel of 24 pancreatic adenocarcinoma cell lines and 13 primary tumor specimens. This high-resolution genomic analysis has identified all known regional gains and losses as well as many previously uncharacterized highly recurrent copy number alterations. A systematic prioritization scheme has selected 64 focal minimal common regions (MCRs) of recurrent copy number change. These MCRs possess a median size of 2.7 megabases (Mb), with 21 (33%) MCRs spanning 1 Mb or less (median of 0.33 Mb) and possessing an average of 15 annotated genes. Furthermore, complementary expression profile analysis of a significant fraction of the genes residing within these 64 prioritized MCRs has enabled the identification of a subset of candidates with statistically significant association between gene dosage and mRNA expression. Thus, the integration of DNA and RNA profiles provides a highly productive entry point for the discovery of genes involved in the pathogenesis of pancreatic adenocarcinoma.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.0402932101</identifier><identifier>PMID: 15199222</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Adenocarcinoma ; Adenocarcinoma - genetics ; Animals ; Biological Sciences ; Cancer ; Cell Line, Tumor ; Cell lines ; Chromosomes ; Chromosomes - genetics ; Chromosomes, Human, Pair 17 ; Comparative genomic hybridization ; Computational Biology - methods ; Cyclin-Dependent Kinase Inhibitor p16 - genetics ; Gene Deletion ; Gene Dosage ; Gene Expression ; Genes ; Genetic loci ; Genome ; Genomes ; Genomics ; Homozygote ; Humans ; Medical research ; Nucleic Acid Hybridization - methods ; Oligonucleotide Array Sequence Analysis ; Pancreas ; Pancreatic Neoplasms - genetics ; Tumor cell line ; Tumors</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2004-06, Vol.101 (24), p.9067-9072</ispartof><rights>Copyright 1993/2004 The National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Jun 15, 2004</rights><rights>Copyright © 2004, The National Academy of Sciences 2004</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c590t-f2a6eb60da3e743bda2021ef5c339b784154fd971d00a07dabe1080f9e8486023</citedby><cites>FETCH-LOGICAL-c590t-f2a6eb60da3e743bda2021ef5c339b784154fd971d00a07dabe1080f9e8486023</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/101/24.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/3372391$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/3372391$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,315,729,782,786,805,887,27931,27932,53798,53800,58024,58257</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15199222$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Aguirre, Andrew J.</creatorcontrib><creatorcontrib>Brennan, Cameron</creatorcontrib><creatorcontrib>Bailey, Gerald</creatorcontrib><creatorcontrib>Sinha, Raktim</creatorcontrib><creatorcontrib>Feng, Bin</creatorcontrib><creatorcontrib>Leo, Christopher</creatorcontrib><creatorcontrib>Zhang, Yunyu</creatorcontrib><creatorcontrib>Zhang, Jean</creatorcontrib><creatorcontrib>Gans, Joseph D.</creatorcontrib><creatorcontrib>Bardeesy, Nabeel</creatorcontrib><creatorcontrib>Cauwels, Craig</creatorcontrib><creatorcontrib>Cordon-Cardo, Carlos</creatorcontrib><creatorcontrib>Redston, Mark S.</creatorcontrib><creatorcontrib>DePinho, Ronald A.</creatorcontrib><creatorcontrib>Chin, Lynda</creatorcontrib><creatorcontrib>Cantley, Lewis C.</creatorcontrib><title>High-Resolution Characterization of the Pancreatic Adenocarcinoma Genome</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>The pancreatic adenocarcinoma genome harbors multiple amplifications and deletions, pointing to the existence of numerous oncogenes and tumor suppressor genes driving the genesis and progression of this lethal cancer. Here, array comparative genomic hybridization on a cDNA microarray platform and informatics tools have been used to define the copy number alterations in a panel of 24 pancreatic adenocarcinoma cell lines and 13 primary tumor specimens. This high-resolution genomic analysis has identified all known regional gains and losses as well as many previously uncharacterized highly recurrent copy number alterations. A systematic prioritization scheme has selected 64 focal minimal common regions (MCRs) of recurrent copy number change. These MCRs possess a median size of 2.7 megabases (Mb), with 21 (33%) MCRs spanning 1 Mb or less (median of 0.33 Mb) and possessing an average of 15 annotated genes. Furthermore, complementary expression profile analysis of a significant fraction of the genes residing within these 64 prioritized MCRs has enabled the identification of a subset of candidates with statistically significant association between gene dosage and mRNA expression. Thus, the integration of DNA and RNA profiles provides a highly productive entry point for the discovery of genes involved in the pathogenesis of pancreatic adenocarcinoma.</description><subject>Adenocarcinoma</subject><subject>Adenocarcinoma - genetics</subject><subject>Animals</subject><subject>Biological Sciences</subject><subject>Cancer</subject><subject>Cell Line, Tumor</subject><subject>Cell lines</subject><subject>Chromosomes</subject><subject>Chromosomes - genetics</subject><subject>Chromosomes, Human, Pair 17</subject><subject>Comparative genomic hybridization</subject><subject>Computational Biology - methods</subject><subject>Cyclin-Dependent Kinase Inhibitor p16 - genetics</subject><subject>Gene Deletion</subject><subject>Gene Dosage</subject><subject>Gene Expression</subject><subject>Genes</subject><subject>Genetic loci</subject><subject>Genome</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Homozygote</subject><subject>Humans</subject><subject>Medical research</subject><subject>Nucleic Acid Hybridization - methods</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Pancreas</subject><subject>Pancreatic Neoplasms - genetics</subject><subject>Tumor cell line</subject><subject>Tumors</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1v1DAQxS1ERZeFMxcEEQfUS9rxR-L40EO1Kl2kSiAEZ8txJt2sknixHQT89XXYVRc4wMnyzO89e-YR8oLCOQXJL3ajCecggCnOKNBHZEFB0bwUCh6TBQCTeSWYOCVPQ9gCgCoqeEJOaUGVYowtyHrd3W3yTxhcP8XOjdlqY7yxEX330_wquDaLG8w-mtF6TCWbXTU4Omu87UY3mOwm3QZ8Rk5a0wd8fjiX5Mu768-rdX774eb96uo2t4WCmLfMlFiX0BiOUvC6MQwYxbawnKtaVoIWom2UpA2AAdmYGilU0CqsRFUC40tyuffdTfWAjcUxetPrne8G439oZzr9Z2fsNvrOfdOCVSK9uCRvD3rvvk4Yoh66YLHvzYhuCloy4KWkxX9BWqV1cqUS-OYvcOsmP6YlaAZ0TkbObhd7yHoXgsf24ccU9BylnqPUxyiT4tXvgx75Q3YJODsAs_JoRzUTWkEpdTv1fcTvMaGv_40m4uWe2Ibo_APCuWRcUX4Pwum78Q</recordid><startdate>20040615</startdate><enddate>20040615</enddate><creator>Aguirre, Andrew J.</creator><creator>Brennan, Cameron</creator><creator>Bailey, Gerald</creator><creator>Sinha, Raktim</creator><creator>Feng, Bin</creator><creator>Leo, Christopher</creator><creator>Zhang, Yunyu</creator><creator>Zhang, Jean</creator><creator>Gans, Joseph D.</creator><creator>Bardeesy, Nabeel</creator><creator>Cauwels, Craig</creator><creator>Cordon-Cardo, Carlos</creator><creator>Redston, Mark S.</creator><creator>DePinho, Ronald A.</creator><creator>Chin, Lynda</creator><creator>Cantley, Lewis C.</creator><general>National Academy of Sciences</general><general>National Acad Sciences</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>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20040615</creationdate><title>High-Resolution Characterization of the Pancreatic Adenocarcinoma Genome</title><author>Aguirre, Andrew J. ; 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Here, array comparative genomic hybridization on a cDNA microarray platform and informatics tools have been used to define the copy number alterations in a panel of 24 pancreatic adenocarcinoma cell lines and 13 primary tumor specimens. This high-resolution genomic analysis has identified all known regional gains and losses as well as many previously uncharacterized highly recurrent copy number alterations. A systematic prioritization scheme has selected 64 focal minimal common regions (MCRs) of recurrent copy number change. These MCRs possess a median size of 2.7 megabases (Mb), with 21 (33%) MCRs spanning 1 Mb or less (median of 0.33 Mb) and possessing an average of 15 annotated genes. Furthermore, complementary expression profile analysis of a significant fraction of the genes residing within these 64 prioritized MCRs has enabled the identification of a subset of candidates with statistically significant association between gene dosage and mRNA expression. Thus, the integration of DNA and RNA profiles provides a highly productive entry point for the discovery of genes involved in the pathogenesis of pancreatic adenocarcinoma.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>15199222</pmid><doi>10.1073/pnas.0402932101</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adenocarcinoma Adenocarcinoma - genetics Animals Biological Sciences Cancer Cell Line, Tumor Cell lines Chromosomes Chromosomes - genetics Chromosomes, Human, Pair 17 Comparative genomic hybridization Computational Biology - methods Cyclin-Dependent Kinase Inhibitor p16 - genetics Gene Deletion Gene Dosage Gene Expression Genes Genetic loci Genome Genomes Genomics Homozygote Humans Medical research Nucleic Acid Hybridization - methods Oligonucleotide Array Sequence Analysis Pancreas Pancreatic Neoplasms - genetics Tumor cell line Tumors |
| title | High-Resolution Characterization of the Pancreatic Adenocarcinoma Genome |
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