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Article: Somatic mutations of the protein kinase gene family in human lung cancer

TitleSomatic mutations of the protein kinase gene family in human lung cancer
Authors
Issue Date2005
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/
Citation
Cancer Research, 2005, v. 65 n. 17, p. 7591-7595 How to Cite?
AbstractProtein kinases are frequently mutated in human cancer and inhibitors of mutant protein kinases have proven to be effective anticancer drugs. We screened the coding sequences of 518 protein kinases (∼1.3 Mb of DNA per sample) for somatic mutations in 26 primary lung neoplasms and seven lung cancer cell lines. One hundred eighty-eight somatic mutations were detected in 141 genes. Of these, 35 were synonymous (silent) changes. This result indicates that most of the 188 mutations were passenger mutations that are not causally implicated in oncogenesis. However, an excess of ∼40 nonsynonymous substitutions compared with that expected by chance (P = 0.07) suggests that some nonsynonymous mutations have been selected and are contributing to oncogenesis. There was considerable variation between individual lung cancers in the number of mutations observed and no mutations were found in lung carcinoids. The mutational spectra of most lung cancers were characterized by a high proportion of C:G > A:T transversions, compatible with the mutagenic effects of tobacco carcinogens. However, one neuroendocrine cancer cell line had a distinctive mutational spectrum reminiscent of UV-induced DNA damage. The results suggest that several mutated protein kinases may be contributing to lung cancer development, but that mutations in each one are infrequent. ©2005 American Association for Cancer Research.
Persistent Identifierhttp://hdl.handle.net/10722/88671
ISSN
2015 Impact Factor: 8.556
2015 SCImago Journal Rankings: 5.372
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorDavies, Hen_HK
dc.contributor.authorHunter, Cen_HK
dc.contributor.authorSmith, Ren_HK
dc.contributor.authorStephens, Pen_HK
dc.contributor.authorGreenman, Cen_HK
dc.contributor.authorBignell, Gen_HK
dc.contributor.authorTeague, Jen_HK
dc.contributor.authorButler, Aen_HK
dc.contributor.authorEdkins, Sen_HK
dc.contributor.authorStevens, Cen_HK
dc.contributor.authorParker, Aen_HK
dc.contributor.authorO'Meara, Sen_HK
dc.contributor.authorAvis, Ten_HK
dc.contributor.authorBarthorpe, Sen_HK
dc.contributor.authorBrackenbury, Len_HK
dc.contributor.authorBuck, Gen_HK
dc.contributor.authorClements, Jen_HK
dc.contributor.authorCole, Jen_HK
dc.contributor.authorDicks, Een_HK
dc.contributor.authorEdwards, Ken_HK
dc.contributor.authorForbes, Sen_HK
dc.contributor.authorGorton, Men_HK
dc.contributor.authorGray, Ken_HK
dc.contributor.authorHalliday, Ken_HK
dc.contributor.authorHarrison, Ren_HK
dc.contributor.authorHills, Ken_HK
dc.contributor.authorHinton, Jen_HK
dc.contributor.authorJones, Den_HK
dc.contributor.authorKosmidou, Ven_HK
dc.contributor.authorLaman, Ren_HK
dc.contributor.authorLugg, Ren_HK
dc.contributor.authorMenzies, Aen_HK
dc.contributor.authorPerry, Jen_HK
dc.contributor.authorPetty, Ren_HK
dc.contributor.authorRaine, Ken_HK
dc.contributor.authorShepherd, Ren_HK
dc.contributor.authorSmall, Aen_HK
dc.contributor.authorSolomon, Hen_HK
dc.contributor.authorStephens, Yen_HK
dc.contributor.authorTofts, Cen_HK
dc.contributor.authorVarian, Jen_HK
dc.contributor.authorWebb, Aen_HK
dc.contributor.authorWest, Sen_HK
dc.contributor.authorWidaa, Sen_HK
dc.contributor.authorYates, Aen_HK
dc.contributor.authorBrasseur, Fen_HK
dc.contributor.authorCooper, CSen_HK
dc.contributor.authorFlanagan, AMen_HK
dc.contributor.authorGreen, Aen_HK
dc.contributor.authorKnowles, Men_HK
dc.contributor.authorLeung, SYen_HK
dc.contributor.authorLooijenga, LHJen_HK
dc.contributor.authorMalkowicz, Ben_HK
dc.contributor.authorPierotti, MAen_HK
dc.contributor.authorTeh, BTen_HK
dc.contributor.authorYuen, STen_HK
dc.contributor.authorLakhani, SRen_HK
dc.contributor.authorEaston, DFen_HK
dc.contributor.authorWeber, BLen_HK
dc.contributor.authorGoldstraw, Pen_HK
dc.contributor.authorNicholson, AGen_HK
dc.contributor.authorWooster, Ren_HK
dc.contributor.authorStratton, MRen_HK
dc.contributor.authorFutreal, PAen_HK
dc.date.accessioned2010-09-06T09:46:26Z-
dc.date.available2010-09-06T09:46:26Z-
dc.date.issued2005en_HK
dc.identifier.citationCancer Research, 2005, v. 65 n. 17, p. 7591-7595en_HK
dc.identifier.issn0008-5472en_HK
dc.identifier.urihttp://hdl.handle.net/10722/88671-
dc.description.abstractProtein kinases are frequently mutated in human cancer and inhibitors of mutant protein kinases have proven to be effective anticancer drugs. We screened the coding sequences of 518 protein kinases (∼1.3 Mb of DNA per sample) for somatic mutations in 26 primary lung neoplasms and seven lung cancer cell lines. One hundred eighty-eight somatic mutations were detected in 141 genes. Of these, 35 were synonymous (silent) changes. This result indicates that most of the 188 mutations were passenger mutations that are not causally implicated in oncogenesis. However, an excess of ∼40 nonsynonymous substitutions compared with that expected by chance (P = 0.07) suggests that some nonsynonymous mutations have been selected and are contributing to oncogenesis. There was considerable variation between individual lung cancers in the number of mutations observed and no mutations were found in lung carcinoids. The mutational spectra of most lung cancers were characterized by a high proportion of C:G > A:T transversions, compatible with the mutagenic effects of tobacco carcinogens. However, one neuroendocrine cancer cell line had a distinctive mutational spectrum reminiscent of UV-induced DNA damage. The results suggest that several mutated protein kinases may be contributing to lung cancer development, but that mutations in each one are infrequent. ©2005 American Association for Cancer Research.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 - enzymology - geneticsen_HK
dc.subject.meshCarcinoid Tumor - enzymology - geneticsen_HK
dc.subject.meshCarcinoma, Large Cell - enzymology - geneticsen_HK
dc.subject.meshCarcinoma, Squamous Cell - enzymology - geneticsen_HK
dc.subject.meshCell Line, Tumoren_HK
dc.subject.meshDNA Mutational Analysisen_HK
dc.subject.meshHumansen_HK
dc.subject.meshLung Neoplasms - enzymology - geneticsen_HK
dc.subject.meshMutationen_HK
dc.subject.meshProtein Kinases - geneticsen_HK
dc.titleSomatic mutations of the protein kinase gene family in human lung canceren_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0008-5472&volume=65&issue=17&spage=7591&epage=5&date=2005&atitle=Somatic+mutations+of+the+protein+kinase+gene+family+in+human+lung+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.doi10.1158/0008-5472.CAN-05-1855en_HK
dc.identifier.pmid16140923-
dc.identifier.scopuseid_2-s2.0-24744453982en_HK
dc.identifier.hkuros113967en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-24744453982&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume65en_HK
dc.identifier.issue17en_HK
dc.identifier.spage7591en_HK
dc.identifier.epage7595en_HK
dc.identifier.isiWOS:000231659500012-
dc.publisher.placeUnited Statesen_HK
dc.identifier.citeulike2735276-

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