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

Davies, Helen, Hunter, Chris, Smith, Raffaella, Stephens, Philip, Greenman, Christopher, Bignell, Graham, Teague, Jon, Butler, Adam, Edkins, Sarah, Stevens, Claire, Parker, Adrian, O'Meara, Sarah, Avis, Tim, Barthorpe, Syd, Brackenbury, Lisa, Buck, Gemma, Clements, Jody, Cole, Jennifer, Dicks, Ed, Edwards, Ken, Forbes, Simon, Gorton, Matthew, Gray, Kristian, Halliday, Kelly, Harrison, Rachel, Hills, Katy, Hinton, Jonathon, Jones, David, Kosmidou, Vivienne, Laman, Ross, Lugg, Richard, Menzies, Andrew, Perry, Janet, Petty, Robert, Raine, Keiran, Shepherd, Rebecca, Small, Alexandra, Solomon, Helen, Stephens, Yvonne, Tofts, Calli, Varian, Jennifer, Webb, Anthony, West, Sofie, Widaa, Sara, Yates, Andrew, Brasseur, Francis, Cooper, Colin S ORCID: https://orcid.org/0000-0003-2013-8042, Flanagan, Adrienne M, Green, Anthony, Knowles, Maggie, Leung, Suet Y, Looijenga, Leendert H J, Malkowicz, Bruce, Pierotti, Marco A, Teh, Bin T, Yuen, Siu T, Lakhani, Sunil R, Easton, Douglas F, Weber, Barbara L, Goldstraw, Peter, Nicholson, Andrew G, Wooster, Richard, Stratton, Michael R and Futreal, P Andrew (2005) Somatic mutations of the protein kinase gene family in human lung cancer. Cancer Research, 65 (17). pp. 7591-5. ISSN 0008-5472

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Abstract

Protein 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 (approximately 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 approximately 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.

Item Type:	Article
Uncontrolled Keywords:	adenocarcinoma,carcinoid tumor,carcinoma, large cell,carcinoma, squamous cell,cell line, tumor,dna mutational analysis,humans,lung neoplasms,mutation,protein kinases,sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School:	Faculty of Science > School of Computing Sciences Faculty of Medicine and Health Sciences > School of Rehabilitation Sciences (former - to 2014) Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups:	Faculty of Science > Research Groups > Computational Biology Faculty of Medicine and Health Sciences > Research Groups > Cancer Studies
Depositing User:	Pure Connector
Date Deposited:	20 Jan 2014 16:00
Last Modified:	18 Apr 2023 23:54
URI:	https://ueaeprints.uea.ac.uk/id/eprint/46159
DOI:	10.1158/0008-5472.CAN-05-1855

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