High resolution genomic analysis of sporadic breast cancer using array-based comparative genomic hybridization
Genomic aberrations in the form of subchromosomal DNA copy number changes are a hallmark of epithelial cancers, including breast cancer. The goal of the present study was to analyze such aberrations in breast cancer at high resolution. We employed high-resolution array comparative genomic hybridizat...
Gespeichert in:
| Veröffentlicht in: | Breast cancer research : BCR 2005-01, Vol.7 (6), p.R1186-R1198, Article R1186 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | R1198 |
|---|---|
| container_issue | 6 |
| container_start_page | R1186 |
| container_title | Breast cancer research : BCR |
| container_volume | 7 |
| creator | Naylor, Tara L Greshock, Joel Wang, Yan Colligon, Theresa Yu, Q C Clemmer, Virginia Zaks, Tal Z Weber, Barbara L |
| description | Genomic aberrations in the form of subchromosomal DNA copy number changes are a hallmark of epithelial cancers, including breast cancer. The goal of the present study was to analyze such aberrations in breast cancer at high resolution.
We employed high-resolution array comparative genomic hybridization with 4,134 bacterial artificial chromosomes that cover the genome at 0.9 megabase resolution to analyze 47 primary breast tumors and 18 breast cancer cell lines.
Common amplicons included 8q24.3 (amplified in 79% of tumors, with 5/47 exhibiting high level amplification), 1q32.1 and 16p13.3 (amplified in 66% and 57% of tumors, respectively). Moreover, we found several positive correlations between specific amplicons from different chromosomes, suggesting the existence of cooperating genetic loci. Queried by gene, the most frequently amplified kinase was PTK2 (79% of tumors), whereas the most frequently lost kinase was PTK2B (hemizygous loss in 34% of tumors). Amplification of ERBB2 as measured by comparative genomic hybridization (CGH) correlated closely with ERBB2 DNA and RNA levels measured by quantitative PCR as well as with ERBB2 protein levels. The overall frequency of recurrent losses was lower, with no region lost in more than 50% of tumors; the most frequently lost tumor suppressor gene was RB1 (hemizygous loss in 26% of tumors). Finally, we find that specific copy number changes in cell lines closely mimicked those in primary tumors, with an overall Pearson correlation coefficient of 0.843 for gains and 0.734 for losses.
High resolution CGH analysis of breast cancer reveals several regions where DNA copy number is commonly gained or lost, that non-random correlations between specific amplicons exist, and that specific genetic alterations are maintained in breast cancer cell lines despite repeat passage in tissue culture. These observations suggest that genes within these regions are critical to the malignant phenotype and may thus serve as future therapeutic targets. |
| doi_str_mv | 10.1186/bcr1356 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_1410746</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A511365104</galeid><sourcerecordid>A511365104</sourcerecordid><originalsourceid>FETCH-LOGICAL-b550t-1f1edf723bb36253a819c782a485eb91126f558e1cac91fff8daeec7bc0e5d813</originalsourceid><addsrcrecordid>eNp1kt-L1DAQx4Mo3rmK_4EUH_SpZ6Zt0taHg-NQTzjwRcG3MEknuznaZE3ag_WvN8su557gU4aZ73zmR4ax18AvADr5QZsItZBP2Dk0UpSiqX4-PbHP2IuU7jiHthPdc3YGshGt7Ptz5m_celNESmFcZhd8sSYfJmcK9DjukktFsEXahohDdupImObCoDcUiyU5vy4wRtyVGhMNhQnTFiPO7p4eQJudjm5wv3GPf8meWRwTvTq-K_bj86fv1zfl7bcvX6-vbkstBJ9LsECDbata61pWosYOetN2FTadIN0DVNIK0REYND1Ya7sBiUyrDScxdFCv2OWBu130RIMhP0cc1Ta6CeNOBXTqccS7jVqHewUN8LaRGfDxANAu_AfwOJJHV8dfyMnvjtVj-LVQmtXkkqFxRE9hSarlUPGqEVn49h_hXVhi3nxSVS255E29p10cRGscSTlvQy6YB8eB8n6DJ-uy_0oA1FJATlmx94cEE0NKkexD28DV_lxOGn1zuqa_uuN91H8ADwLAEA</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>236060436</pqid></control><display><type>article</type><title>High resolution genomic analysis of sporadic breast cancer using array-based comparative genomic hybridization</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central Open Access</source><source>Springer Nature OA Free Journals</source><source>PubMed Central</source><source>SpringerLink Journals - AutoHoldings</source><creator>Naylor, Tara L ; Greshock, Joel ; Wang, Yan ; Colligon, Theresa ; Yu, Q C ; Clemmer, Virginia ; Zaks, Tal Z ; Weber, Barbara L</creator><creatorcontrib>Naylor, Tara L ; Greshock, Joel ; Wang, Yan ; Colligon, Theresa ; Yu, Q C ; Clemmer, Virginia ; Zaks, Tal Z ; Weber, Barbara L</creatorcontrib><description>Genomic aberrations in the form of subchromosomal DNA copy number changes are a hallmark of epithelial cancers, including breast cancer. The goal of the present study was to analyze such aberrations in breast cancer at high resolution.
We employed high-resolution array comparative genomic hybridization with 4,134 bacterial artificial chromosomes that cover the genome at 0.9 megabase resolution to analyze 47 primary breast tumors and 18 breast cancer cell lines.
Common amplicons included 8q24.3 (amplified in 79% of tumors, with 5/47 exhibiting high level amplification), 1q32.1 and 16p13.3 (amplified in 66% and 57% of tumors, respectively). Moreover, we found several positive correlations between specific amplicons from different chromosomes, suggesting the existence of cooperating genetic loci. Queried by gene, the most frequently amplified kinase was PTK2 (79% of tumors), whereas the most frequently lost kinase was PTK2B (hemizygous loss in 34% of tumors). Amplification of ERBB2 as measured by comparative genomic hybridization (CGH) correlated closely with ERBB2 DNA and RNA levels measured by quantitative PCR as well as with ERBB2 protein levels. The overall frequency of recurrent losses was lower, with no region lost in more than 50% of tumors; the most frequently lost tumor suppressor gene was RB1 (hemizygous loss in 26% of tumors). Finally, we find that specific copy number changes in cell lines closely mimicked those in primary tumors, with an overall Pearson correlation coefficient of 0.843 for gains and 0.734 for losses.
High resolution CGH analysis of breast cancer reveals several regions where DNA copy number is commonly gained or lost, that non-random correlations between specific amplicons exist, and that specific genetic alterations are maintained in breast cancer cell lines despite repeat passage in tissue culture. These observations suggest that genes within these regions are critical to the malignant phenotype and may thus serve as future therapeutic targets.</description><identifier>ISSN: 1465-542X</identifier><identifier>ISSN: 1465-5411</identifier><identifier>EISSN: 1465-542X</identifier><identifier>DOI: 10.1186/bcr1356</identifier><identifier>PMID: 16457699</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Analysis ; Breast cancer ; Breast Neoplasms - genetics ; Cell Line, Tumor ; Chromosomes, Artificial, Bacterial - genetics ; DNA, Neoplasm - genetics ; Female ; Focal Adhesion Kinase 1 - genetics ; Gene Dosage ; Gene Expression Profiling ; Genomics ; Humans ; Hybridization ; Nucleic Acid Hybridization ; Oligonucleotide Array Sequence Analysis ; Phenotype ; Receptor, ErbB-2 - genetics ; Sensitivity and Specificity</subject><ispartof>Breast cancer research : BCR, 2005-01, Vol.7 (6), p.R1186-R1198, Article R1186</ispartof><rights>COPYRIGHT 2005 BioMed Central Ltd.</rights><rights>Copyright National Library of Medicine - MEDLINE Abstracts 2005</rights><rights>Copyright © 2005 Naylor et al.; licensee BioMed Central Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b550t-1f1edf723bb36253a819c782a485eb91126f558e1cac91fff8daeec7bc0e5d813</citedby><cites>FETCH-LOGICAL-b550t-1f1edf723bb36253a819c782a485eb91126f558e1cac91fff8daeec7bc0e5d813</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/PMC1410746/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1410746/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16457699$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Naylor, Tara L</creatorcontrib><creatorcontrib>Greshock, Joel</creatorcontrib><creatorcontrib>Wang, Yan</creatorcontrib><creatorcontrib>Colligon, Theresa</creatorcontrib><creatorcontrib>Yu, Q C</creatorcontrib><creatorcontrib>Clemmer, Virginia</creatorcontrib><creatorcontrib>Zaks, Tal Z</creatorcontrib><creatorcontrib>Weber, Barbara L</creatorcontrib><title>High resolution genomic analysis of sporadic breast cancer using array-based comparative genomic hybridization</title><title>Breast cancer research : BCR</title><addtitle>Breast Cancer Res</addtitle><description>Genomic aberrations in the form of subchromosomal DNA copy number changes are a hallmark of epithelial cancers, including breast cancer. The goal of the present study was to analyze such aberrations in breast cancer at high resolution.
We employed high-resolution array comparative genomic hybridization with 4,134 bacterial artificial chromosomes that cover the genome at 0.9 megabase resolution to analyze 47 primary breast tumors and 18 breast cancer cell lines.
Common amplicons included 8q24.3 (amplified in 79% of tumors, with 5/47 exhibiting high level amplification), 1q32.1 and 16p13.3 (amplified in 66% and 57% of tumors, respectively). Moreover, we found several positive correlations between specific amplicons from different chromosomes, suggesting the existence of cooperating genetic loci. Queried by gene, the most frequently amplified kinase was PTK2 (79% of tumors), whereas the most frequently lost kinase was PTK2B (hemizygous loss in 34% of tumors). Amplification of ERBB2 as measured by comparative genomic hybridization (CGH) correlated closely with ERBB2 DNA and RNA levels measured by quantitative PCR as well as with ERBB2 protein levels. The overall frequency of recurrent losses was lower, with no region lost in more than 50% of tumors; the most frequently lost tumor suppressor gene was RB1 (hemizygous loss in 26% of tumors). Finally, we find that specific copy number changes in cell lines closely mimicked those in primary tumors, with an overall Pearson correlation coefficient of 0.843 for gains and 0.734 for losses.
High resolution CGH analysis of breast cancer reveals several regions where DNA copy number is commonly gained or lost, that non-random correlations between specific amplicons exist, and that specific genetic alterations are maintained in breast cancer cell lines despite repeat passage in tissue culture. These observations suggest that genes within these regions are critical to the malignant phenotype and may thus serve as future therapeutic targets.</description><subject>Analysis</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - genetics</subject><subject>Cell Line, Tumor</subject><subject>Chromosomes, Artificial, Bacterial - genetics</subject><subject>DNA, Neoplasm - genetics</subject><subject>Female</subject><subject>Focal Adhesion Kinase 1 - genetics</subject><subject>Gene Dosage</subject><subject>Gene Expression Profiling</subject><subject>Genomics</subject><subject>Humans</subject><subject>Hybridization</subject><subject>Nucleic Acid Hybridization</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Phenotype</subject><subject>Receptor, ErbB-2 - genetics</subject><subject>Sensitivity and Specificity</subject><issn>1465-542X</issn><issn>1465-5411</issn><issn>1465-542X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kt-L1DAQx4Mo3rmK_4EUH_SpZ6Zt0taHg-NQTzjwRcG3MEknuznaZE3ag_WvN8su557gU4aZ73zmR4ax18AvADr5QZsItZBP2Dk0UpSiqX4-PbHP2IuU7jiHthPdc3YGshGt7Ptz5m_celNESmFcZhd8sSYfJmcK9DjukktFsEXahohDdupImObCoDcUiyU5vy4wRtyVGhMNhQnTFiPO7p4eQJudjm5wv3GPf8meWRwTvTq-K_bj86fv1zfl7bcvX6-vbkstBJ9LsECDbata61pWosYOetN2FTadIN0DVNIK0REYND1Ya7sBiUyrDScxdFCv2OWBu130RIMhP0cc1Ta6CeNOBXTqccS7jVqHewUN8LaRGfDxANAu_AfwOJJHV8dfyMnvjtVj-LVQmtXkkqFxRE9hSarlUPGqEVn49h_hXVhi3nxSVS255E29p10cRGscSTlvQy6YB8eB8n6DJ-uy_0oA1FJATlmx94cEE0NKkexD28DV_lxOGn1zuqa_uuN91H8ADwLAEA</recordid><startdate>20050101</startdate><enddate>20050101</enddate><creator>Naylor, Tara L</creator><creator>Greshock, Joel</creator><creator>Wang, Yan</creator><creator>Colligon, Theresa</creator><creator>Yu, Q C</creator><creator>Clemmer, Virginia</creator><creator>Zaks, Tal Z</creator><creator>Weber, Barbara L</creator><general>BioMed Central Ltd</general><general>National Library of Medicine - MEDLINE Abstracts</general><general>BioMed Central</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>K9.</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20050101</creationdate><title>High resolution genomic analysis of sporadic breast cancer using array-based comparative genomic hybridization</title><author>Naylor, Tara L ; Greshock, Joel ; Wang, Yan ; Colligon, Theresa ; Yu, Q C ; Clemmer, Virginia ; Zaks, Tal Z ; Weber, Barbara L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b550t-1f1edf723bb36253a819c782a485eb91126f558e1cac91fff8daeec7bc0e5d813</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Analysis</topic><topic>Breast cancer</topic><topic>Breast Neoplasms - genetics</topic><topic>Cell Line, Tumor</topic><topic>Chromosomes, Artificial, Bacterial - genetics</topic><topic>DNA, Neoplasm - genetics</topic><topic>Female</topic><topic>Focal Adhesion Kinase 1 - genetics</topic><topic>Gene Dosage</topic><topic>Gene Expression Profiling</topic><topic>Genomics</topic><topic>Humans</topic><topic>Hybridization</topic><topic>Nucleic Acid Hybridization</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>Phenotype</topic><topic>Receptor, ErbB-2 - genetics</topic><topic>Sensitivity and Specificity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Naylor, Tara L</creatorcontrib><creatorcontrib>Greshock, Joel</creatorcontrib><creatorcontrib>Wang, Yan</creatorcontrib><creatorcontrib>Colligon, Theresa</creatorcontrib><creatorcontrib>Yu, Q C</creatorcontrib><creatorcontrib>Clemmer, Virginia</creatorcontrib><creatorcontrib>Zaks, Tal Z</creatorcontrib><creatorcontrib>Weber, Barbara L</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 Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Breast cancer research : BCR</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Naylor, Tara L</au><au>Greshock, Joel</au><au>Wang, Yan</au><au>Colligon, Theresa</au><au>Yu, Q C</au><au>Clemmer, Virginia</au><au>Zaks, Tal Z</au><au>Weber, Barbara L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>High resolution genomic analysis of sporadic breast cancer using array-based comparative genomic hybridization</atitle><jtitle>Breast cancer research : BCR</jtitle><addtitle>Breast Cancer Res</addtitle><date>2005-01-01</date><risdate>2005</risdate><volume>7</volume><issue>6</issue><spage>R1186</spage><epage>R1198</epage><pages>R1186-R1198</pages><artnum>R1186</artnum><issn>1465-542X</issn><issn>1465-5411</issn><eissn>1465-542X</eissn><abstract>Genomic aberrations in the form of subchromosomal DNA copy number changes are a hallmark of epithelial cancers, including breast cancer. The goal of the present study was to analyze such aberrations in breast cancer at high resolution.
We employed high-resolution array comparative genomic hybridization with 4,134 bacterial artificial chromosomes that cover the genome at 0.9 megabase resolution to analyze 47 primary breast tumors and 18 breast cancer cell lines.
Common amplicons included 8q24.3 (amplified in 79% of tumors, with 5/47 exhibiting high level amplification), 1q32.1 and 16p13.3 (amplified in 66% and 57% of tumors, respectively). Moreover, we found several positive correlations between specific amplicons from different chromosomes, suggesting the existence of cooperating genetic loci. Queried by gene, the most frequently amplified kinase was PTK2 (79% of tumors), whereas the most frequently lost kinase was PTK2B (hemizygous loss in 34% of tumors). Amplification of ERBB2 as measured by comparative genomic hybridization (CGH) correlated closely with ERBB2 DNA and RNA levels measured by quantitative PCR as well as with ERBB2 protein levels. The overall frequency of recurrent losses was lower, with no region lost in more than 50% of tumors; the most frequently lost tumor suppressor gene was RB1 (hemizygous loss in 26% of tumors). Finally, we find that specific copy number changes in cell lines closely mimicked those in primary tumors, with an overall Pearson correlation coefficient of 0.843 for gains and 0.734 for losses.
High resolution CGH analysis of breast cancer reveals several regions where DNA copy number is commonly gained or lost, that non-random correlations between specific amplicons exist, and that specific genetic alterations are maintained in breast cancer cell lines despite repeat passage in tissue culture. These observations suggest that genes within these regions are critical to the malignant phenotype and may thus serve as future therapeutic targets.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>16457699</pmid><doi>10.1186/bcr1356</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1465-542X |
| ispartof | Breast cancer research : BCR, 2005-01, Vol.7 (6), p.R1186-R1198, Article R1186 |
| issn | 1465-542X 1465-5411 1465-542X |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_1410746 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central Open Access; Springer Nature OA Free Journals; PubMed Central; SpringerLink Journals - AutoHoldings |
| subjects | Analysis Breast cancer Breast Neoplasms - genetics Cell Line, Tumor Chromosomes, Artificial, Bacterial - genetics DNA, Neoplasm - genetics Female Focal Adhesion Kinase 1 - genetics Gene Dosage Gene Expression Profiling Genomics Humans Hybridization Nucleic Acid Hybridization Oligonucleotide Array Sequence Analysis Phenotype Receptor, ErbB-2 - genetics Sensitivity and Specificity |
| title | High resolution genomic analysis of sporadic breast cancer using array-based comparative genomic hybridization |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-05T05%3A00%3A42IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=High%20resolution%20genomic%20analysis%20of%20sporadic%20breast%20cancer%20using%20array-based%20comparative%20genomic%20hybridization&rft.jtitle=Breast%20cancer%20research%20:%20BCR&rft.au=Naylor,%20Tara%20L&rft.date=2005-01-01&rft.volume=7&rft.issue=6&rft.spage=R1186&rft.epage=R1198&rft.pages=R1186-R1198&rft.artnum=R1186&rft.issn=1465-542X&rft.eissn=1465-542X&rft_id=info:doi/10.1186/bcr1356&rft_dat=%3Cgale_pubme%3EA511365104%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=236060436&rft_id=info:pmid/16457699&rft_galeid=A511365104&rfr_iscdi=true |