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Article: Activating Smoothened mutations in sporadic basal-cell carcinoma

TitleActivating Smoothened mutations in sporadic basal-cell carcinoma
Authors
Issue Date1998
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/nature
Citation
Nature, 1998, v. 391 n. 6662, p. 90-92 How to Cite?
AbstractBasal-cell carcinomas (BCCs) are the commonest human cancer. Insight into their genesis came from identification of mutations in the PATCHED gene (PTCH) in patients with the basal-cell nevus syndrome, a hereditary disease characterized by multiple BCCs and by developmental abnormalities. The binding of Sonic hedgehog (SHH) to its receptor, PTCH, is thought to prevent normal inhibition by PTCH of Smoothened (SMO), a seven-span transmembrane protein. According to this model, the inhibition of SMO signalling is relieved following mutational inactivation of PTGH in basal-cell nevus syndrome. We report here the identification of activating somatic missense mutations in the SMO gene itself in sporadic BCCs from three patients. Mutant SMO, unlike wild type, can cooperate with adenovirus E1A to transform rat embryonic fibroblast cells in culture. Furthermore, skin abnormalities similar to BCCs developed in transgenic murine skin overexpressing mutant SMO. These findings support the role of SMO as a signalling component of the SHH-receptor complex and provide direct evidence that mutated SMO can function as an oncogene in BCCs.
Persistent Identifierhttp://hdl.handle.net/10722/148117
ISSN
2015 Impact Factor: 38.138
2015 SCImago Journal Rankings: 21.936
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorXie, Jen_US
dc.contributor.authorMurone, Men_US
dc.contributor.authorLuoh, SMen_US
dc.contributor.authorRyan, Aen_US
dc.contributor.authorGu, Qen_US
dc.contributor.authorZhang, Cen_US
dc.contributor.authorBonifas, JMen_US
dc.contributor.authorLam, CWen_US
dc.contributor.authorHynes, Men_US
dc.contributor.authorGoddard, Aen_US
dc.contributor.authorRosenthal, Aen_US
dc.contributor.authorEpstein Jr, EHen_US
dc.contributor.authorDe Sauvage, FJen_US
dc.date.accessioned2012-05-29T06:10:56Z-
dc.date.available2012-05-29T06:10:56Z-
dc.date.issued1998en_US
dc.identifier.citationNature, 1998, v. 391 n. 6662, p. 90-92en_US
dc.identifier.issn0028-0836en_US
dc.identifier.urihttp://hdl.handle.net/10722/148117-
dc.description.abstractBasal-cell carcinomas (BCCs) are the commonest human cancer. Insight into their genesis came from identification of mutations in the PATCHED gene (PTCH) in patients with the basal-cell nevus syndrome, a hereditary disease characterized by multiple BCCs and by developmental abnormalities. The binding of Sonic hedgehog (SHH) to its receptor, PTCH, is thought to prevent normal inhibition by PTCH of Smoothened (SMO), a seven-span transmembrane protein. According to this model, the inhibition of SMO signalling is relieved following mutational inactivation of PTGH in basal-cell nevus syndrome. We report here the identification of activating somatic missense mutations in the SMO gene itself in sporadic BCCs from three patients. Mutant SMO, unlike wild type, can cooperate with adenovirus E1A to transform rat embryonic fibroblast cells in culture. Furthermore, skin abnormalities similar to BCCs developed in transgenic murine skin overexpressing mutant SMO. These findings support the role of SMO as a signalling component of the SHH-receptor complex and provide direct evidence that mutated SMO can function as an oncogene in BCCs.en_US
dc.languageengen_US
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/natureen_US
dc.relation.ispartofNatureen_US
dc.subject.meshAdenovirus E1a Proteins - Genetics - Physiologyen_US
dc.subject.meshAnimalsen_US
dc.subject.meshCarcinoma, Basal Cell - Geneticsen_US
dc.subject.meshCell Lineen_US
dc.subject.meshChromosome Mappingen_US
dc.subject.meshChromosomes, Human, Pair 7en_US
dc.subject.meshHedgehog Proteinsen_US
dc.subject.meshHumansen_US
dc.subject.meshIntracellular Signaling Peptides And Proteinsen_US
dc.subject.meshMembrane Proteins - Genetics - Metabolismen_US
dc.subject.meshMiceen_US
dc.subject.meshMice, Transgenicen_US
dc.subject.meshMutationen_US
dc.subject.meshOncogenesen_US
dc.subject.meshPolymerase Chain Reactionen_US
dc.subject.meshProtein Conformationen_US
dc.subject.meshProteins - Metabolismen_US
dc.subject.meshRatsen_US
dc.subject.meshReceptors, Cell Surface - Chemistry - Genetics - Physiologyen_US
dc.subject.meshReceptors, G-Protein-Coupleden_US
dc.subject.meshSignal Transductionen_US
dc.subject.meshSkin Neoplasms - Geneticsen_US
dc.subject.meshTrans-Activatorsen_US
dc.subject.meshTransfectionen_US
dc.titleActivating Smoothened mutations in sporadic basal-cell carcinomaen_US
dc.typeArticleen_US
dc.identifier.emailLam, CW:ching-wanlam@pathology.hku.hken_US
dc.identifier.authorityLam, CW=rp00260en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1038/34201en_US
dc.identifier.pmid9422511-
dc.identifier.scopuseid_2-s2.0-0031913524en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0031913524&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume391en_US
dc.identifier.issue6662en_US
dc.identifier.spage90en_US
dc.identifier.epage92en_US
dc.identifier.isiWOS:000071326100055-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.citeulike8877214-

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