High-throughput tissue microarray analysis of 3p25 (RAF1) and 8p12 (FGFR1) copy number alterations in urinary bladder cancer
Studies by comparative genomic hybridization revealed that the chromosomal regions 3p25 and 8p11-p12 are recurrently amplified in bladder cancer. To investigate the prevalence of DNA copy number alterations in these chromosomal regions and study their clinical significance, we used probes for the RA...
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| Veröffentlicht in: | Cancer research (Chicago, Ill.) Ill.), 2001-06, Vol.61 (11), p.4514-4519 |
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| creator | SIMON, Ronald RICHTER, Jan RIST, Marcus WILBER, Kim ANABITARTE, Manuel HERING, Franz HARDMEIER, Thomas SCHÖNENBERGER, Andreas FLURY, Renata JÄGER, Peter FEHR, Jean Luc SCHRAML, Peter WAGNER, Urs MOCH, Holger MIHATSCH, Michael J GASSER, Thomas SAUTER, Guido FIJAN, André BRUDERER, James SCHMID, Ulrico ACKERMANN, Daniel MAURER, Robert ALUND, Göran KNÖNAGEL, Hartmut |
| description | Studies by comparative genomic hybridization revealed that the chromosomal regions 3p25 and 8p11-p12 are recurrently amplified in bladder cancer. To investigate the prevalence of DNA copy number alterations in these chromosomal regions and study their clinical significance, we used probes for the RAF1 (3p25) and FGFR1 (8p12) genes for fluorescence in situ hybridization. A tissue microarray containing 2317 tumors was analyzed. The analysis revealed RAF1 amplification in 4.0% and FGFR1 amplification in 3.4% of interpretable tumors. In addition, deletions were found at the 3p25 locus in 2.2% and at the 8p11-12 locus in 9.9% of interpretable tumors. Both amplifications and deletions of RAF1 and FGFR1 were significantly associated with high tumor grade (P < 0.0001), advanced stage (P < 0.0001), and poor survival (P < 0.05) if tumors of all of the stages where analyzed together. RAF1 amplifications were associated with subsequent tumor progression in pT1 carcinomas (P < 0.05). The marked differences in the frequency of all of the analyzed changes between pTa grade 1/grade 2 and pT1-4 carcinomas support the concept of these tumor groups representing different tumor entities. |
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To investigate the prevalence of DNA copy number alterations in these chromosomal regions and study their clinical significance, we used probes for the RAF1 (3p25) and FGFR1 (8p12) genes for fluorescence in situ hybridization. A tissue microarray containing 2317 tumors was analyzed. The analysis revealed RAF1 amplification in 4.0% and FGFR1 amplification in 3.4% of interpretable tumors. In addition, deletions were found at the 3p25 locus in 2.2% and at the 8p11-12 locus in 9.9% of interpretable tumors. Both amplifications and deletions of RAF1 and FGFR1 were significantly associated with high tumor grade (P < 0.0001), advanced stage (P < 0.0001), and poor survival (P < 0.05) if tumors of all of the stages where analyzed together. RAF1 amplifications were associated with subsequent tumor progression in pT1 carcinomas (P < 0.05). The marked differences in the frequency of all of the analyzed changes between pTa grade 1/grade 2 and pT1-4 carcinomas support the concept of these tumor groups representing different tumor entities.</description><identifier>ISSN: 0008-5472</identifier><identifier>EISSN: 1538-7445</identifier><identifier>PMID: 11389083</identifier><identifier>CODEN: CNREA8</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Biological and medical sciences ; chromosome 3 ; chromosome 8 ; Chromosomes, Human, Pair 3 - genetics ; Chromosomes, Human, Pair 8 - genetics ; FGFR1 gene ; Gene Amplification ; Gene Deletion ; Gene Dosage ; Humans ; In Situ Hybridization, Fluorescence ; Medical sciences ; Neoplasm Staging ; Nephrology. Urinary tract diseases ; Prognosis ; Proto-Oncogene Proteins c-raf - genetics ; RAF1 gene ; Receptor Protein-Tyrosine Kinases - genetics ; Receptor, Fibroblast Growth Factor, Type 1 ; Receptors, Fibroblast Growth Factor - genetics ; Retrospective Studies ; Tumors of the urinary system ; Urinary Bladder Neoplasms - genetics ; Urinary Bladder Neoplasms - pathology ; Urinary tract. Prostate gland</subject><ispartof>Cancer research (Chicago, Ill.), 2001-06, Vol.61 (11), p.4514-4519</ispartof><rights>2001 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1067493$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11389083$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>SIMON, Ronald</creatorcontrib><creatorcontrib>RICHTER, Jan</creatorcontrib><creatorcontrib>RIST, Marcus</creatorcontrib><creatorcontrib>WILBER, Kim</creatorcontrib><creatorcontrib>ANABITARTE, Manuel</creatorcontrib><creatorcontrib>HERING, Franz</creatorcontrib><creatorcontrib>HARDMEIER, Thomas</creatorcontrib><creatorcontrib>SCHÖNENBERGER, Andreas</creatorcontrib><creatorcontrib>FLURY, Renata</creatorcontrib><creatorcontrib>JÄGER, Peter</creatorcontrib><creatorcontrib>FEHR, Jean Luc</creatorcontrib><creatorcontrib>SCHRAML, Peter</creatorcontrib><creatorcontrib>WAGNER, Urs</creatorcontrib><creatorcontrib>MOCH, Holger</creatorcontrib><creatorcontrib>MIHATSCH, Michael J</creatorcontrib><creatorcontrib>GASSER, Thomas</creatorcontrib><creatorcontrib>SAUTER, Guido</creatorcontrib><creatorcontrib>FIJAN, André</creatorcontrib><creatorcontrib>BRUDERER, James</creatorcontrib><creatorcontrib>SCHMID, Ulrico</creatorcontrib><creatorcontrib>ACKERMANN, Daniel</creatorcontrib><creatorcontrib>MAURER, Robert</creatorcontrib><creatorcontrib>ALUND, Göran</creatorcontrib><creatorcontrib>KNÖNAGEL, Hartmut</creatorcontrib><title>High-throughput tissue microarray analysis of 3p25 (RAF1) and 8p12 (FGFR1) copy number alterations in urinary bladder cancer</title><title>Cancer research (Chicago, Ill.)</title><addtitle>Cancer Res</addtitle><description>Studies by comparative genomic hybridization revealed that the chromosomal regions 3p25 and 8p11-p12 are recurrently amplified in bladder cancer. To investigate the prevalence of DNA copy number alterations in these chromosomal regions and study their clinical significance, we used probes for the RAF1 (3p25) and FGFR1 (8p12) genes for fluorescence in situ hybridization. A tissue microarray containing 2317 tumors was analyzed. The analysis revealed RAF1 amplification in 4.0% and FGFR1 amplification in 3.4% of interpretable tumors. In addition, deletions were found at the 3p25 locus in 2.2% and at the 8p11-12 locus in 9.9% of interpretable tumors. Both amplifications and deletions of RAF1 and FGFR1 were significantly associated with high tumor grade (P < 0.0001), advanced stage (P < 0.0001), and poor survival (P < 0.05) if tumors of all of the stages where analyzed together. RAF1 amplifications were associated with subsequent tumor progression in pT1 carcinomas (P < 0.05). The marked differences in the frequency of all of the analyzed changes between pTa grade 1/grade 2 and pT1-4 carcinomas support the concept of these tumor groups representing different tumor entities.</description><subject>Biological and medical sciences</subject><subject>chromosome 3</subject><subject>chromosome 8</subject><subject>Chromosomes, Human, Pair 3 - genetics</subject><subject>Chromosomes, Human, Pair 8 - genetics</subject><subject>FGFR1 gene</subject><subject>Gene Amplification</subject><subject>Gene Deletion</subject><subject>Gene Dosage</subject><subject>Humans</subject><subject>In Situ Hybridization, Fluorescence</subject><subject>Medical sciences</subject><subject>Neoplasm Staging</subject><subject>Nephrology. Urinary tract diseases</subject><subject>Prognosis</subject><subject>Proto-Oncogene Proteins c-raf - genetics</subject><subject>RAF1 gene</subject><subject>Receptor Protein-Tyrosine Kinases - genetics</subject><subject>Receptor, Fibroblast Growth Factor, Type 1</subject><subject>Receptors, Fibroblast Growth Factor - genetics</subject><subject>Retrospective Studies</subject><subject>Tumors of the urinary system</subject><subject>Urinary Bladder Neoplasms - genetics</subject><subject>Urinary Bladder Neoplasms - pathology</subject><subject>Urinary tract. Prostate gland</subject><issn>0008-5472</issn><issn>1538-7445</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0E1LxDAQBuAgiruu_gXJQWQ9FCZJ2zTHZbGusCAsei5pmm4j_TJpDgV_vBFXPHoaZuZh4J0ztCQJyyIex8k5WgJAFiUxpwt05dx7aBMCySVaEMIyARlbos-dOTbR1NjBH5vRT3gyznmNO6PsIK2VM5a9bGdnHB5qzEaa4PVhk5OHMK9wNhKK1_lTfggDNYwz7n1XaotlO2krJzP0Dpsee2t6aWdctrKqwlrJXml7jS5q2Tp9c6or9JY_vm530f7l6Xm72UcNJekUUcpoChxUWbMyriBOSaVrWYISFIgSpQaiA0gZBVGlSa0VB53xODAggrAVuv-5O9rhw2s3FZ1xSret7PXgXcFBABVc_AsJzwRJyffF2xP0ZaerYrSmC_mK38cGcHcC0inZ1jYENu7PQcpjwdgX5COAPg</recordid><startdate>20010601</startdate><enddate>20010601</enddate><creator>SIMON, Ronald</creator><creator>RICHTER, Jan</creator><creator>RIST, Marcus</creator><creator>WILBER, Kim</creator><creator>ANABITARTE, Manuel</creator><creator>HERING, Franz</creator><creator>HARDMEIER, Thomas</creator><creator>SCHÖNENBERGER, Andreas</creator><creator>FLURY, Renata</creator><creator>JÄGER, Peter</creator><creator>FEHR, Jean Luc</creator><creator>SCHRAML, Peter</creator><creator>WAGNER, Urs</creator><creator>MOCH, Holger</creator><creator>MIHATSCH, Michael J</creator><creator>GASSER, Thomas</creator><creator>SAUTER, Guido</creator><creator>FIJAN, André</creator><creator>BRUDERER, James</creator><creator>SCHMID, Ulrico</creator><creator>ACKERMANN, Daniel</creator><creator>MAURER, Robert</creator><creator>ALUND, Göran</creator><creator>KNÖNAGEL, Hartmut</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>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20010601</creationdate><title>High-throughput tissue microarray analysis of 3p25 (RAF1) and 8p12 (FGFR1) copy number alterations in urinary bladder cancer</title><author>SIMON, Ronald ; RICHTER, Jan ; RIST, Marcus ; WILBER, Kim ; ANABITARTE, Manuel ; HERING, Franz ; HARDMEIER, Thomas ; SCHÖNENBERGER, Andreas ; FLURY, Renata ; JÄGER, Peter ; FEHR, Jean Luc ; SCHRAML, Peter ; WAGNER, Urs ; MOCH, Holger ; MIHATSCH, Michael J ; GASSER, Thomas ; SAUTER, Guido ; FIJAN, André ; BRUDERER, James ; SCHMID, Ulrico ; ACKERMANN, Daniel ; MAURER, Robert ; ALUND, Göran ; KNÖNAGEL, Hartmut</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h216t-22326070cbf3b4d0461defab0c9201c9be01e60763209d65fec70e8741de01913</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Biological and medical sciences</topic><topic>chromosome 3</topic><topic>chromosome 8</topic><topic>Chromosomes, Human, Pair 3 - genetics</topic><topic>Chromosomes, Human, Pair 8 - genetics</topic><topic>FGFR1 gene</topic><topic>Gene Amplification</topic><topic>Gene Deletion</topic><topic>Gene Dosage</topic><topic>Humans</topic><topic>In Situ Hybridization, Fluorescence</topic><topic>Medical sciences</topic><topic>Neoplasm Staging</topic><topic>Nephrology. Urinary tract diseases</topic><topic>Prognosis</topic><topic>Proto-Oncogene Proteins c-raf - genetics</topic><topic>RAF1 gene</topic><topic>Receptor Protein-Tyrosine Kinases - genetics</topic><topic>Receptor, Fibroblast Growth Factor, Type 1</topic><topic>Receptors, Fibroblast Growth Factor - genetics</topic><topic>Retrospective Studies</topic><topic>Tumors of the urinary system</topic><topic>Urinary Bladder Neoplasms - genetics</topic><topic>Urinary Bladder Neoplasms - pathology</topic><topic>Urinary tract. 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To investigate the prevalence of DNA copy number alterations in these chromosomal regions and study their clinical significance, we used probes for the RAF1 (3p25) and FGFR1 (8p12) genes for fluorescence in situ hybridization. A tissue microarray containing 2317 tumors was analyzed. The analysis revealed RAF1 amplification in 4.0% and FGFR1 amplification in 3.4% of interpretable tumors. In addition, deletions were found at the 3p25 locus in 2.2% and at the 8p11-12 locus in 9.9% of interpretable tumors. Both amplifications and deletions of RAF1 and FGFR1 were significantly associated with high tumor grade (P < 0.0001), advanced stage (P < 0.0001), and poor survival (P < 0.05) if tumors of all of the stages where analyzed together. RAF1 amplifications were associated with subsequent tumor progression in pT1 carcinomas (P < 0.05). The marked differences in the frequency of all of the analyzed changes between pTa grade 1/grade 2 and pT1-4 carcinomas support the concept of these tumor groups representing different tumor entities.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>11389083</pmid><tpages>6</tpages></addata></record> |
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| subjects | Biological and medical sciences chromosome 3 chromosome 8 Chromosomes, Human, Pair 3 - genetics Chromosomes, Human, Pair 8 - genetics FGFR1 gene Gene Amplification Gene Deletion Gene Dosage Humans In Situ Hybridization, Fluorescence Medical sciences Neoplasm Staging Nephrology. Urinary tract diseases Prognosis Proto-Oncogene Proteins c-raf - genetics RAF1 gene Receptor Protein-Tyrosine Kinases - genetics Receptor, Fibroblast Growth Factor, Type 1 Receptors, Fibroblast Growth Factor - genetics Retrospective Studies Tumors of the urinary system Urinary Bladder Neoplasms - genetics Urinary Bladder Neoplasms - pathology Urinary tract. Prostate gland |
| title | High-throughput tissue microarray analysis of 3p25 (RAF1) and 8p12 (FGFR1) copy number alterations in urinary bladder cancer |
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