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Article: Mutations of the BRAF gene in human cancer

TitleMutations of the BRAF gene in human cancer
Authors
Issue Date2002
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/nature
Citation
Nature, 2002, v. 417 n. 6892, p. 949-954 How to Cite?
AbstractCancers arise owing to the accumulation of mutations in critical genes that alter normal programmes of cell proliferation, differentiation and death. As the first stage of a systematic genomewide screen for these genes, we have prioritized for analysis signalling pathways in which at least one gene is mutated in human cancer. The RAS-RAF-MEK-ERK-MAP kinase pathway mediates cellular responses to growth signals1. RAS is mutated to an oncogenic form in about 15% of human cancer. The three RAF genes code for cytoplasmic serine/threonine kinases that are regulated by binding RAS1-3. Here we report BRAF somatic missense mutations in 66% of malignant melanomas and at lower frequency in a wide range of human cancers. All mutations are within the kinase domain, with a single substitution (V599E) accounting for 80%. Mutated BRAF proteins have elevated kinase activity and are transforming in NIH3T3 cells. Furthermore, RAS function is not required for the growth of cancer cell lines with the V599E mutation. As BRAF is a serine/threonine kinase that is commonly activated by somatic point mutation in human cancer, it may provide new therapeutic opportunities in malignant melanoma.
Persistent Identifierhttp://hdl.handle.net/10722/88754
ISSN
2015 Impact Factor: 38.138
2015 SCImago Journal Rankings: 21.936
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorDavies, Hen_HK
dc.contributor.authorBignell, GRen_HK
dc.contributor.authorCox, Cen_HK
dc.contributor.authorStephens, Pen_HK
dc.contributor.authorEdkins, Sen_HK
dc.contributor.authorClegg, Sen_HK
dc.contributor.authorTeague, Jen_HK
dc.contributor.authorWoffendin, Hen_HK
dc.contributor.authorGarnett, MJen_HK
dc.contributor.authorBottomley, Wen_HK
dc.contributor.authorDavis, Nen_HK
dc.contributor.authorDicks, Een_HK
dc.contributor.authorEwing, Ren_HK
dc.contributor.authorFloyd, Yen_HK
dc.contributor.authorGray, Ken_HK
dc.contributor.authorHall, Sen_HK
dc.contributor.authorHawes, Ren_HK
dc.contributor.authorHughes, Jen_HK
dc.contributor.authorKosmidou, Ven_HK
dc.contributor.authorMenzies, Aen_HK
dc.contributor.authorMould, Cen_HK
dc.contributor.authorParker, Aen_HK
dc.contributor.authorStevens, Cen_HK
dc.contributor.authorWatt, Sen_HK
dc.contributor.authorHooper, Sen_HK
dc.contributor.authorWilson, Ren_HK
dc.contributor.authorJayatilake, Hen_HK
dc.contributor.authorGusterson, BAen_HK
dc.contributor.authorCooper, Cen_HK
dc.contributor.authorShipley, Jen_HK
dc.contributor.authorHargrave, Den_HK
dc.contributor.authorPritchardJones, Ken_HK
dc.contributor.authorMaitland, Nen_HK
dc.contributor.authorChenevixTrench, Gen_HK
dc.contributor.authorRiggins, GJen_HK
dc.contributor.authorBigner, DDen_HK
dc.contributor.authorPalmleri, Gen_HK
dc.contributor.authorCossu, Aen_HK
dc.contributor.authorFlanagan, Aen_HK
dc.contributor.authorNicholson, Aen_HK
dc.contributor.authorHo, JWCen_HK
dc.contributor.authorLeung, SYen_HK
dc.contributor.authorYuen, STen_HK
dc.contributor.authorWeber, BLen_HK
dc.contributor.authorSeigler, HFen_HK
dc.contributor.authorDarrow, TLen_HK
dc.contributor.authorPaterson, Hen_HK
dc.contributor.authorMarais, Ren_HK
dc.contributor.authorMarshall, CJen_HK
dc.contributor.authorWooster, Ren_HK
dc.contributor.authorStratton, MRen_HK
dc.contributor.authorFutreal, PAen_HK
dc.date.accessioned2010-09-06T09:47:32Z-
dc.date.available2010-09-06T09:47:32Z-
dc.date.issued2002en_HK
dc.identifier.citationNature, 2002, v. 417 n. 6892, p. 949-954en_HK
dc.identifier.issn0028-0836en_HK
dc.identifier.urihttp://hdl.handle.net/10722/88754-
dc.description.abstractCancers arise owing to the accumulation of mutations in critical genes that alter normal programmes of cell proliferation, differentiation and death. As the first stage of a systematic genomewide screen for these genes, we have prioritized for analysis signalling pathways in which at least one gene is mutated in human cancer. The RAS-RAF-MEK-ERK-MAP kinase pathway mediates cellular responses to growth signals1. RAS is mutated to an oncogenic form in about 15% of human cancer. The three RAF genes code for cytoplasmic serine/threonine kinases that are regulated by binding RAS1-3. Here we report BRAF somatic missense mutations in 66% of malignant melanomas and at lower frequency in a wide range of human cancers. All mutations are within the kinase domain, with a single substitution (V599E) accounting for 80%. Mutated BRAF proteins have elevated kinase activity and are transforming in NIH3T3 cells. Furthermore, RAS function is not required for the growth of cancer cell lines with the V599E mutation. As BRAF is a serine/threonine kinase that is commonly activated by somatic point mutation in human cancer, it may provide new therapeutic opportunities in malignant melanoma.en_HK
dc.languageengen_HK
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/natureen_HK
dc.relation.ispartofNatureen_HK
dc.subject.mesh3T3 Cellsen_HK
dc.subject.meshAmino Acid Sequenceen_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshBase Sequenceen_HK
dc.subject.meshCell Divisionen_HK
dc.subject.meshCell Transformation, Neoplastic - geneticsen_HK
dc.subject.meshDNA Mutational Analysisen_HK
dc.subject.meshEnzyme Activationen_HK
dc.subject.meshHumansen_HK
dc.subject.meshMAP Kinase Signaling Systemen_HK
dc.subject.meshMelanoma - enzymology - genetics - metabolism - pathologyen_HK
dc.subject.meshMiceen_HK
dc.subject.meshMitogen-Activated Protein Kinases - metabolismen_HK
dc.subject.meshMolecular Sequence Dataen_HK
dc.subject.meshMutation, Missense - geneticsen_HK
dc.subject.meshNeoplasms - enzymology - genetics - metabolism - pathologyen_HK
dc.subject.meshProtein Structure, Tertiaryen_HK
dc.subject.meshProto-Oncogene Proteins B-rafen_HK
dc.subject.meshProto-Oncogene Proteins c-raf - chemistry - genetics - metabolismen_HK
dc.subject.meshTumor Cells, Cultureden_HK
dc.subject.meshras Proteins - immunology - metabolismen_HK
dc.titleMutations of the BRAF gene in human canceren_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0028-0836&volume=417&spage=949&epage=954&date=2002&atitle=Mutations+of+the+BRAF+gene+in+human+canceren_HK
dc.identifier.emailLeung, SY:suetyi@hkucc.hku.hken_HK
dc.identifier.authorityLeung, SY=rp00359en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1038/nature00766en_HK
dc.identifier.pmid12068308-
dc.identifier.scopuseid_2-s2.0-18444374405en_HK
dc.identifier.hkuros67398en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-18444374405&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume417en_HK
dc.identifier.issue6892en_HK
dc.identifier.spage949en_HK
dc.identifier.epage954en_HK
dc.identifier.isiWOS:000176441200039-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.f10001007413-
dc.identifier.citeulike1272192-

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