Somatic Mutations of Epidermal Growth Factor Receptor in Colorectal Carcinoma
Purpose: Somatic mutations of the epidermal growth factor receptor (EGFR) gene may predict the sensitivity of non–small cell lung carcinoma to gefitinib. However, no mutations have been reported for colorectal carcinoma. We therefore analyzed EGFR mutations in colorectal adenocarcinomas by the combi...
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Veröffentlicht in: | Clinical cancer research 2005-02, Vol.11 (4), p.1368-1371 |
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creator | NAGAHARA, Hisashi MIMORI, Koshi OHTA, Mitsuhiko UTSUNOMIYA, Tohru INOUE, Hiroshi BARNARD, Graham F OHIRA, Masaichi HIRAKAWA, Kosei MORI, Masaki |
description | Purpose: Somatic mutations of the epidermal growth factor receptor (EGFR) gene may predict the sensitivity of non–small cell lung
carcinoma to gefitinib. However, no mutations have been reported for colorectal carcinoma. We therefore analyzed EGFR mutations
in colorectal adenocarcinomas by the combined use of laser microdissection and sequencing of genomic DNA.
Experimental Design: We examined 11 representative colorectal adenocarcinoma cell lines and 33 clinical samples of colorectal carcinoma. In the
clinical cases, we carefully dissected only carcinoma cells from frozen sections by laser microdissection. After DNA extraction
and PCR, we examined EGFR mutations by sequencing genomic DNA.
Results: None of 11 colorectal carcinoma cell lines exhibited somatic mutations, but 4 of 33 clinical tumors (12%) exhibited mutations
in the EGFR kinase domain. This may be the first report of somatic mutations in colorectal adenocarcinoma.
Conclusions: Our findings suggest that a distinct minority of colorectal adenocarcinomas exhibit somatic mutations of EGFR, and these
tumors may be susceptible to gefitinib treatment. |
doi_str_mv | 10.1158/1078-0432.CCR-04-1894 |
format | Article |
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carcinoma to gefitinib. However, no mutations have been reported for colorectal carcinoma. We therefore analyzed EGFR mutations
in colorectal adenocarcinomas by the combined use of laser microdissection and sequencing of genomic DNA.
Experimental Design: We examined 11 representative colorectal adenocarcinoma cell lines and 33 clinical samples of colorectal carcinoma. In the
clinical cases, we carefully dissected only carcinoma cells from frozen sections by laser microdissection. After DNA extraction
and PCR, we examined EGFR mutations by sequencing genomic DNA.
Results: None of 11 colorectal carcinoma cell lines exhibited somatic mutations, but 4 of 33 clinical tumors (12%) exhibited mutations
in the EGFR kinase domain. This may be the first report of somatic mutations in colorectal adenocarcinoma.
Conclusions: Our findings suggest that a distinct minority of colorectal adenocarcinomas exhibit somatic mutations of EGFR, and these
tumors may be susceptible to gefitinib treatment.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>DOI: 10.1158/1078-0432.CCR-04-1894</identifier><identifier>PMID: 15746034</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>anti-EGFR antibody ; Antineoplastic agents ; Base Sequence ; Biological and medical sciences ; Cell Line, Tumor ; cetuximab ; Colorectal Neoplasms - genetics ; Colorectal Neoplasms - pathology ; DNA Mutational Analysis ; DNA, Neoplasm - chemistry ; DNA, Neoplasm - genetics ; Exons - genetics ; Gastroenterology. Liver. Pancreas. Abdomen ; gefitinib ; HT29 Cells ; Humans ; Medical sciences ; Mutation ; Mutation, Missense ; Pharmacology. Drug treatments ; Receptor, Epidermal Growth Factor - genetics ; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus ; Tumors</subject><ispartof>Clinical cancer research, 2005-02, Vol.11 (4), p.1368-1371</ispartof><rights>2005 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c514t-9262797533f4c53f8cdac5127f42ed5b3a32860bb3fc7cee848586cfd9d30ca93</citedby><cites>FETCH-LOGICAL-c514t-9262797533f4c53f8cdac5127f42ed5b3a32860bb3fc7cee848586cfd9d30ca93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,3356,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16560420$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15746034$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>NAGAHARA, Hisashi</creatorcontrib><creatorcontrib>MIMORI, Koshi</creatorcontrib><creatorcontrib>OHTA, Mitsuhiko</creatorcontrib><creatorcontrib>UTSUNOMIYA, Tohru</creatorcontrib><creatorcontrib>INOUE, Hiroshi</creatorcontrib><creatorcontrib>BARNARD, Graham F</creatorcontrib><creatorcontrib>OHIRA, Masaichi</creatorcontrib><creatorcontrib>HIRAKAWA, Kosei</creatorcontrib><creatorcontrib>MORI, Masaki</creatorcontrib><title>Somatic Mutations of Epidermal Growth Factor Receptor in Colorectal Carcinoma</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>Purpose: Somatic mutations of the epidermal growth factor receptor (EGFR) gene may predict the sensitivity of non–small cell lung
carcinoma to gefitinib. However, no mutations have been reported for colorectal carcinoma. We therefore analyzed EGFR mutations
in colorectal adenocarcinomas by the combined use of laser microdissection and sequencing of genomic DNA.
Experimental Design: We examined 11 representative colorectal adenocarcinoma cell lines and 33 clinical samples of colorectal carcinoma. In the
clinical cases, we carefully dissected only carcinoma cells from frozen sections by laser microdissection. After DNA extraction
and PCR, we examined EGFR mutations by sequencing genomic DNA.
Results: None of 11 colorectal carcinoma cell lines exhibited somatic mutations, but 4 of 33 clinical tumors (12%) exhibited mutations
in the EGFR kinase domain. This may be the first report of somatic mutations in colorectal adenocarcinoma.
Conclusions: Our findings suggest that a distinct minority of colorectal adenocarcinomas exhibit somatic mutations of EGFR, and these
tumors may be susceptible to gefitinib treatment.</description><subject>anti-EGFR antibody</subject><subject>Antineoplastic agents</subject><subject>Base Sequence</subject><subject>Biological and medical sciences</subject><subject>Cell Line, Tumor</subject><subject>cetuximab</subject><subject>Colorectal Neoplasms - genetics</subject><subject>Colorectal Neoplasms - pathology</subject><subject>DNA Mutational Analysis</subject><subject>DNA, Neoplasm - chemistry</subject><subject>DNA, Neoplasm - genetics</subject><subject>Exons - genetics</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>gefitinib</subject><subject>HT29 Cells</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Mutation</subject><subject>Mutation, Missense</subject><subject>Pharmacology. Drug treatments</subject><subject>Receptor, Epidermal Growth Factor - genetics</subject><subject>Stomach. Duodenum. Small intestine. Colon. Rectum. Anus</subject><subject>Tumors</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkEtv1DAURi0EoqXlJ4CyAbFJ8dvOEkVtQWqF1Mfa8txcM0ZJPNgZVf33OJpBXbK6n3TPfegQ8oHRC8aU_cqosS2Vgl_0_V0NLbOdfEVOmVKmFVyr1zX_Y07Iu1J-U8oko_ItOWHKSE2FPCW392nyS4Tmdr_UmubSpNBc7uKAefJjc53T07JtrjwsKTd3CLhbQ5ybPo0pIywV6n2GONdF5-RN8GPB98d6Rh6vLh_67-3Nz-sf_bebFhSTS9txzU1nlBBBghLBwuBrh5sgOQ5qI7zgVtPNRgQwgGilVVZDGLpBUPCdOCOfD3t3Of3ZY1ncFAvgOPoZ0744baRlWov_gswITrk0FVQHEHIqJWNwuxwnn58do24V7laZbpXpqvAa3Cq8zn08HthvJhxepo6GK_DpCPgCfgzZzxDLC6eVppLTyn05cNv4a_sUMzqoJOaMBavebX3C1ZtCW_EXSe2Wag</recordid><startdate>20050215</startdate><enddate>20050215</enddate><creator>NAGAHARA, Hisashi</creator><creator>MIMORI, Koshi</creator><creator>OHTA, Mitsuhiko</creator><creator>UTSUNOMIYA, Tohru</creator><creator>INOUE, Hiroshi</creator><creator>BARNARD, Graham F</creator><creator>OHIRA, Masaichi</creator><creator>HIRAKAWA, Kosei</creator><creator>MORI, Masaki</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>AAYXX</scope><scope>CITATION</scope><scope>7TO</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20050215</creationdate><title>Somatic Mutations of Epidermal Growth Factor Receptor in Colorectal Carcinoma</title><author>NAGAHARA, Hisashi ; MIMORI, Koshi ; OHTA, Mitsuhiko ; UTSUNOMIYA, Tohru ; INOUE, Hiroshi ; BARNARD, Graham F ; OHIRA, Masaichi ; HIRAKAWA, Kosei ; MORI, Masaki</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c514t-9262797533f4c53f8cdac5127f42ed5b3a32860bb3fc7cee848586cfd9d30ca93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>anti-EGFR antibody</topic><topic>Antineoplastic agents</topic><topic>Base Sequence</topic><topic>Biological and medical sciences</topic><topic>Cell Line, Tumor</topic><topic>cetuximab</topic><topic>Colorectal Neoplasms - genetics</topic><topic>Colorectal Neoplasms - pathology</topic><topic>DNA Mutational Analysis</topic><topic>DNA, Neoplasm - chemistry</topic><topic>DNA, Neoplasm - genetics</topic><topic>Exons - genetics</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>gefitinib</topic><topic>HT29 Cells</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Mutation</topic><topic>Mutation, Missense</topic><topic>Pharmacology. Drug treatments</topic><topic>Receptor, Epidermal Growth Factor - genetics</topic><topic>Stomach. Duodenum. Small intestine. Colon. Rectum. Anus</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>NAGAHARA, Hisashi</creatorcontrib><creatorcontrib>MIMORI, Koshi</creatorcontrib><creatorcontrib>OHTA, Mitsuhiko</creatorcontrib><creatorcontrib>UTSUNOMIYA, Tohru</creatorcontrib><creatorcontrib>INOUE, Hiroshi</creatorcontrib><creatorcontrib>BARNARD, Graham F</creatorcontrib><creatorcontrib>OHIRA, Masaichi</creatorcontrib><creatorcontrib>HIRAKAWA, Kosei</creatorcontrib><creatorcontrib>MORI, Masaki</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>Oncogenes and Growth Factors Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>NAGAHARA, Hisashi</au><au>MIMORI, Koshi</au><au>OHTA, Mitsuhiko</au><au>UTSUNOMIYA, Tohru</au><au>INOUE, Hiroshi</au><au>BARNARD, Graham F</au><au>OHIRA, Masaichi</au><au>HIRAKAWA, Kosei</au><au>MORI, Masaki</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Somatic Mutations of Epidermal Growth Factor Receptor in Colorectal Carcinoma</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2005-02-15</date><risdate>2005</risdate><volume>11</volume><issue>4</issue><spage>1368</spage><epage>1371</epage><pages>1368-1371</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><abstract>Purpose: Somatic mutations of the epidermal growth factor receptor (EGFR) gene may predict the sensitivity of non–small cell lung
carcinoma to gefitinib. However, no mutations have been reported for colorectal carcinoma. We therefore analyzed EGFR mutations
in colorectal adenocarcinomas by the combined use of laser microdissection and sequencing of genomic DNA.
Experimental Design: We examined 11 representative colorectal adenocarcinoma cell lines and 33 clinical samples of colorectal carcinoma. In the
clinical cases, we carefully dissected only carcinoma cells from frozen sections by laser microdissection. After DNA extraction
and PCR, we examined EGFR mutations by sequencing genomic DNA.
Results: None of 11 colorectal carcinoma cell lines exhibited somatic mutations, but 4 of 33 clinical tumors (12%) exhibited mutations
in the EGFR kinase domain. This may be the first report of somatic mutations in colorectal adenocarcinoma.
Conclusions: Our findings suggest that a distinct minority of colorectal adenocarcinomas exhibit somatic mutations of EGFR, and these
tumors may be susceptible to gefitinib treatment.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>15746034</pmid><doi>10.1158/1078-0432.CCR-04-1894</doi><tpages>4</tpages><oa>free_for_read</oa></addata></record> |
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source | MEDLINE; American Association for Cancer Research; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
subjects | anti-EGFR antibody Antineoplastic agents Base Sequence Biological and medical sciences Cell Line, Tumor cetuximab Colorectal Neoplasms - genetics Colorectal Neoplasms - pathology DNA Mutational Analysis DNA, Neoplasm - chemistry DNA, Neoplasm - genetics Exons - genetics Gastroenterology. Liver. Pancreas. Abdomen gefitinib HT29 Cells Humans Medical sciences Mutation Mutation, Missense Pharmacology. Drug treatments Receptor, Epidermal Growth Factor - genetics Stomach. Duodenum. Small intestine. Colon. Rectum. Anus Tumors |
title | Somatic Mutations of Epidermal Growth Factor Receptor in Colorectal Carcinoma |
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