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Article: Gastrointestinal stromal tumors (GISTs) with KIT and PDGFRA mutations have distinct gene expression profiles

TitleGastrointestinal stromal tumors (GISTs) with KIT and PDGFRA mutations have distinct gene expression profiles
Authors
KeywordsGene expression
GIST
KIT
Microarray
Mutations
PDGFRA
Issue Date2004
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/onc
Citation
Oncogene, 2004, v. 23 n. 47, p. 7780-7790 How to Cite?
AbstractMost GISTs require oncogenic activation of the KIT or PDGFRA receptor tyrosine kinase proteins, and the genomic mechanisms of oncogene activation are heterogeneous. Notably, the kinase mutation type correlates with both tumor biology and imatinib response. For example, GISTs with KIT exon 11 mutations are typically gastric and have excellent imatinib response, whereas those with KIT exon 9 mutations generally arise in the small bowel and are less responsive to imatinib. To identify genes that might contribute to these biological differences, we carried out gene expression profiling of 26 GISTs with known KIT and PDGFRA mutational status. Expression differences were then evaluated further by RNA in situ hybridization, immunohistochemistry, and immunoblotting. Unsupervised hierarchical clustering grouped tumors with similar mutations together, but the distinction between the different groups was not absolute. Differentially expressed genes included ezrin, p70S6K, and PKCs, which are known to have key roles in KIT or PDGFRA signaling, and which might therefore contribute to the distinctive clinicopathological features in GISTs with different mutation types. These gene products could serve as highly selective therapeutic targets in GISTs containing the KIT or PDGFRA mutational types with which they are associated.
Persistent Identifierhttp://hdl.handle.net/10722/88733
ISSN
2015 Impact Factor: 7.932
2015 SCImago Journal Rankings: 4.047
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorSubramanian, Sen_HK
dc.contributor.authorWest, RBen_HK
dc.contributor.authorCorless, CLen_HK
dc.contributor.authorOu, Wen_HK
dc.contributor.authorRubin, BPen_HK
dc.contributor.authorChu, KMen_HK
dc.contributor.authorLeung, SYen_HK
dc.contributor.authorYuen, STen_HK
dc.contributor.authorZhu, Sen_HK
dc.contributor.authorHernandezBoussard, Ten_HK
dc.contributor.authorMontgomery, Ken_HK
dc.contributor.authorNielsen, TOen_HK
dc.contributor.authorPatel, RMen_HK
dc.contributor.authorGoldblum, JRen_HK
dc.contributor.authorHeinrich, MCen_HK
dc.contributor.authorFletcher, JAen_HK
dc.contributor.authorVan De Rijn, Men_HK
dc.date.accessioned2010-09-06T09:47:15Z-
dc.date.available2010-09-06T09:47:15Z-
dc.date.issued2004en_HK
dc.identifier.citationOncogene, 2004, v. 23 n. 47, p. 7780-7790en_HK
dc.identifier.issn0950-9232en_HK
dc.identifier.urihttp://hdl.handle.net/10722/88733-
dc.description.abstractMost GISTs require oncogenic activation of the KIT or PDGFRA receptor tyrosine kinase proteins, and the genomic mechanisms of oncogene activation are heterogeneous. Notably, the kinase mutation type correlates with both tumor biology and imatinib response. For example, GISTs with KIT exon 11 mutations are typically gastric and have excellent imatinib response, whereas those with KIT exon 9 mutations generally arise in the small bowel and are less responsive to imatinib. To identify genes that might contribute to these biological differences, we carried out gene expression profiling of 26 GISTs with known KIT and PDGFRA mutational status. Expression differences were then evaluated further by RNA in situ hybridization, immunohistochemistry, and immunoblotting. Unsupervised hierarchical clustering grouped tumors with similar mutations together, but the distinction between the different groups was not absolute. Differentially expressed genes included ezrin, p70S6K, and PKCs, which are known to have key roles in KIT or PDGFRA signaling, and which might therefore contribute to the distinctive clinicopathological features in GISTs with different mutation types. These gene products could serve as highly selective therapeutic targets in GISTs containing the KIT or PDGFRA mutational types with which they are associated.en_HK
dc.languageengen_HK
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/oncen_HK
dc.relation.ispartofOncogeneen_HK
dc.subjectGene expressionen_HK
dc.subjectGISTen_HK
dc.subjectKITen_HK
dc.subjectMicroarrayen_HK
dc.subjectMutationsen_HK
dc.subjectPDGFRAen_HK
dc.subject.meshAdolescenten_HK
dc.subject.meshChilden_HK
dc.subject.meshChild, Preschoolen_HK
dc.subject.meshCytoskeletal Proteinsen_HK
dc.subject.meshFemaleen_HK
dc.subject.meshGastrointestinal Neoplasms - genetics - pathologyen_HK
dc.subject.meshGene Expression Profilingen_HK
dc.subject.meshHumansen_HK
dc.subject.meshIntestinal Neoplasms - geneticsen_HK
dc.subject.meshMaleen_HK
dc.subject.meshOncogene Proteins - geneticsen_HK
dc.subject.meshOncogenesen_HK
dc.subject.meshPhosphoproteins - geneticsen_HK
dc.subject.meshProtein Kinase C - geneticsen_HK
dc.subject.meshProto-Oncogene Proteins c-kiten_HK
dc.subject.meshReceptor, Platelet-Derived Growth Factor alpha - geneticsen_HK
dc.subject.meshStomach Neoplasms - geneticsen_HK
dc.subject.meshStromal Cells - pathologyen_HK
dc.titleGastrointestinal stromal tumors (GISTs) with KIT and PDGFRA mutations have distinct gene expression profilesen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0950-9232&volume=2004&spage=7780&epage=7790&date=2004&atitle=Gastrointestinal+stromal+tumors+(GISTs)+with+KIT+and+PDGFRA+mutations+have+distinct+gene+expression+profilesen_HK
dc.identifier.emailChu, KM: chukm@hkucc.hku.hken_HK
dc.identifier.emailLeung, SY: suetyi@hkucc.hku.hken_HK
dc.identifier.authorityChu, KM=rp00435en_HK
dc.identifier.authorityLeung, SY=rp00359en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1038/sj.onc.1208056en_HK
dc.identifier.pmid15326474-
dc.identifier.scopuseid_2-s2.0-7644242712en_HK
dc.identifier.hkuros94876en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-7644242712&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume23en_HK
dc.identifier.issue47en_HK
dc.identifier.spage7780en_HK
dc.identifier.epage7790en_HK
dc.identifier.isiWOS:000224331600004-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridSubramanian, S=7202867578en_HK
dc.identifier.scopusauthoridWest, RB=36041739200en_HK
dc.identifier.scopusauthoridCorless, CL=35395023300en_HK
dc.identifier.scopusauthoridOu, W=36794184100en_HK
dc.identifier.scopusauthoridRubin, BP=7201760688en_HK
dc.identifier.scopusauthoridChu, KM=7402453538en_HK
dc.identifier.scopusauthoridLeung, SY=7202044886en_HK
dc.identifier.scopusauthoridYuen, ST=7103160927en_HK
dc.identifier.scopusauthoridZhu, S=7404391784en_HK
dc.identifier.scopusauthoridHernandezBoussard, T=6603503231en_HK
dc.identifier.scopusauthoridMontgomery, K=7102499348en_HK
dc.identifier.scopusauthoridNielsen, TO=7201759696en_HK
dc.identifier.scopusauthoridPatel, RM=36167300600en_HK
dc.identifier.scopusauthoridGoldblum, JR=7007148492en_HK
dc.identifier.scopusauthoridHeinrich, MC=7103077474en_HK
dc.identifier.scopusauthoridFletcher, JA=7402937532en_HK
dc.identifier.scopusauthoridVan De Rijn, M=7005571510en_HK

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