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Article: Similarity of the phenotypic patterns associated with BRAF and KRAS mutations in colorectal neoplasia

TitleSimilarity of the phenotypic patterns associated with BRAF and KRAS mutations in colorectal neoplasia
Authors
Issue Date2002
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/
Citation
Cancer Research, 2002, v. 62 n. 22, p. 6451-6455 How to Cite?
AbstractActivation of the RAS/RAF/extracellular signal-regulated kinase-mitogen-activated protein kinase/extracellular signal-regulated kinase/mitogen-activated protein kinase pathway by RAS mutations is commonly found in human cancers. Recently, we reported that mutation of BRAF provides an alternative route for activation of this signaling pathway and can be found in melanomas, colorectal cancers, and ovarian tumors. Here we perform an extensive characterization of BRAF mutations in a large series of colorectal tumors in various stages of neoplastic transformation. BRAF mutations were found in 11 of 215 (5.1%) colorectal adenocarcinomas, 3 of 108 (2.8%) sporadic adenomas, 1 of 63 (1.6%) adenomas from familial adenomatous polyposis (FAP) patients, and 1 of 3 (33%) hyperplastic polyps. KRAS mutations were detected in 34% of carcinomas, 31% of sporadic adenomas, 9% of FAP adenomas, and no hyperplastic polyps. Eight of 16 BRAF mutations were V599E, the previously described hotspot, and none of these was associated with a KRAS mutation in the same lesion. The remaining eight mutations involve other conserved amino acids in the kinase domain, and 62.5% have a KRAS mutation in the same tumor. Our data suggest that BRAF mutations are, to some extent, biologically similar to RAS mutations in colorectal cancer because both occur at approximately the same stage of the adenoma-carcinoma sequence, both are associated with villous morphology, and both are less common in adenomas from FAP cases. By contrast, colorectal adenocarcinomas with BRAF mutations are associated with early Dukes' tumor stages (P = 0.006) and no such relationship was observed for KRAS mutations. The presence in some colorectal neoplasms of mutations in both BRAF and KRAS suggests that modulation of the RAS-RAF-extracellular signal-regulated kinase-mitogen-activated protein kinase/extracellular signal-regulated kinase/mitogen-activated protein kinase signaling pathway may occur by mutation of multiple components.
Persistent Identifierhttp://hdl.handle.net/10722/88363
ISSN
2015 Impact Factor: 8.556
2015 SCImago Journal Rankings: 5.372
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorYuen, STen_HK
dc.contributor.authorDavies, Hen_HK
dc.contributor.authorChan, TLen_HK
dc.contributor.authorHo, JWen_HK
dc.contributor.authorBignell, GRen_HK
dc.contributor.authorCox, Cen_HK
dc.contributor.authorStephens, Pen_HK
dc.contributor.authorEdkins, Sen_HK
dc.contributor.authorTsui, WWen_HK
dc.contributor.authorAnnie, Sen_HK
dc.contributor.authorChan, Pen_HK
dc.contributor.authorFutreal, Aen_HK
dc.contributor.authorStratton, MRen_HK
dc.contributor.authorWooster, Ren_HK
dc.contributor.authorLeung, SYen_HK
dc.date.accessioned2010-09-06T09:42:24Z-
dc.date.available2010-09-06T09:42:24Z-
dc.date.issued2002en_HK
dc.identifier.citationCancer Research, 2002, v. 62 n. 22, p. 6451-6455en_HK
dc.identifier.issn0008-5472en_HK
dc.identifier.urihttp://hdl.handle.net/10722/88363-
dc.description.abstractActivation of the RAS/RAF/extracellular signal-regulated kinase-mitogen-activated protein kinase/extracellular signal-regulated kinase/mitogen-activated protein kinase pathway by RAS mutations is commonly found in human cancers. Recently, we reported that mutation of BRAF provides an alternative route for activation of this signaling pathway and can be found in melanomas, colorectal cancers, and ovarian tumors. Here we perform an extensive characterization of BRAF mutations in a large series of colorectal tumors in various stages of neoplastic transformation. BRAF mutations were found in 11 of 215 (5.1%) colorectal adenocarcinomas, 3 of 108 (2.8%) sporadic adenomas, 1 of 63 (1.6%) adenomas from familial adenomatous polyposis (FAP) patients, and 1 of 3 (33%) hyperplastic polyps. KRAS mutations were detected in 34% of carcinomas, 31% of sporadic adenomas, 9% of FAP adenomas, and no hyperplastic polyps. Eight of 16 BRAF mutations were V599E, the previously described hotspot, and none of these was associated with a KRAS mutation in the same lesion. The remaining eight mutations involve other conserved amino acids in the kinase domain, and 62.5% have a KRAS mutation in the same tumor. Our data suggest that BRAF mutations are, to some extent, biologically similar to RAS mutations in colorectal cancer because both occur at approximately the same stage of the adenoma-carcinoma sequence, both are associated with villous morphology, and both are less common in adenomas from FAP cases. By contrast, colorectal adenocarcinomas with BRAF mutations are associated with early Dukes' tumor stages (P = 0.006) and no such relationship was observed for KRAS mutations. The presence in some colorectal neoplasms of mutations in both BRAF and KRAS suggests that modulation of the RAS-RAF-extracellular signal-regulated kinase-mitogen-activated protein kinase/extracellular signal-regulated kinase/mitogen-activated protein kinase signaling pathway may occur by mutation of multiple components.en_HK
dc.languageengen_HK
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/en_HK
dc.relation.ispartofCancer Researchen_HK
dc.subject.meshAdenocarcinoma - genetics - pathologyen_HK
dc.subject.meshAdenomatous Polyposis Coli - genetics - pathologyen_HK
dc.subject.meshAdulten_HK
dc.subject.meshAgeden_HK
dc.subject.meshAged, 80 and overen_HK
dc.subject.meshAmino Acid Sequenceen_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshColonic Polyps - genetics - pathologyen_HK
dc.subject.meshColorectal Neoplasms - genetics - pathologyen_HK
dc.subject.meshFemaleen_HK
dc.subject.meshGenes, ras - geneticsen_HK
dc.subject.meshHumansen_HK
dc.subject.meshMaleen_HK
dc.subject.meshMiddle Ageden_HK
dc.subject.meshMolecular Sequence Dataen_HK
dc.subject.meshMutationen_HK
dc.subject.meshNeoplasm Stagingen_HK
dc.subject.meshPhenotypeen_HK
dc.subject.meshProto-Oncogene Proteins B-rafen_HK
dc.subject.meshProto-Oncogene Proteins c-raf - geneticsen_HK
dc.subject.meshSequence Homology, Amino Aciden_HK
dc.titleSimilarity of the phenotypic patterns associated with BRAF and KRAS mutations in colorectal neoplasiaen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0008-5472&volume=62&spage=6451&epage=6455&date=2002&atitle=Similarity+of+the+phenotypic+patterns+associated+with+BRAF+and+KRAS+mutations+in+colorectal+neoplasiaen_HK
dc.identifier.emailChan, TL:tlchan@hku.hken_HK
dc.identifier.emailLeung, SY:suetyi@hkucc.hku.hken_HK
dc.identifier.authorityChan, TL=rp00418en_HK
dc.identifier.authorityLeung, SY=rp00359en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.pmid12438234-
dc.identifier.scopuseid_2-s2.0-0037112438en_HK
dc.identifier.hkuros81982en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0037112438&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume62en_HK
dc.identifier.issue22en_HK
dc.identifier.spage6451en_HK
dc.identifier.epage6455en_HK
dc.identifier.isiWOS:000179315200021-
dc.publisher.placeUnited Statesen_HK

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