Somatic Mutations of the Protein Kinase Gene Family in Human Lung Cancer
Helen Davies,Christopher I. Hunter,Raffaella Smith,Philip J. Stephens,Christopher Greenman,Graham R. Bignell,Jon W. Teague,Adam Butler,Sarah Edkins,Claire Stevens,Adrian Parker,Sarah O’Meara,Tim Avis,Syd Barthorpe,Lisa Brackenbury,Gemma Buck,Jody Clements,Jennifer Cole,Ed Dicks,Ken Edwards,Simon A. Forbes,Matthew Gorton,Kristian Gray,Kelly Halliday,Rachel Harrison,Katy Hills,Jonathon Hinton,David Jones,Vivienne Kosmidou,Ross Laman,Richard Lugg,Andrew Menzies,Janet Perry,Robert Petty,Keiran Raine,Rebecca Shepherd,Alexandra Small,Helen Solomon,Yvonne Stephens,Calli Tofts,Jennifer Varian,Anthony Webb,Sofie West,Sara Widaa,Andrew D. Yates,Francis Brasseur,Colin Cooper,Adrienne M. Flanagan,Anthony R. Green,Maggie Knowles,Suet Yi Leung,Leendert H. J. Looijenga,Bruce Malkowicz,Marco A. Pierotti,Bin Tean Teh,Siu Tsan Yuen,Sunil R. Lakhani,Douglas F. Easton,Barbara L. Weber,Peter Goldstraw,Andrew G. Nicholson,Richard Wooster,Richard Wooster,Michael R. Stratton,P. Andrew Futreal +64 more
TLDR
The results suggest that several mutated protein kinases may be contributing to lung cancer development, but that mutations in each one are infrequent.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.read more
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The landscape of somatic copy-number alteration across human cancers
Rameen Beroukhim,Craig H. Mermel,Craig H. Mermel,Dale Porter,Guo Wei,Soumya Raychaudhuri,Soumya Raychaudhuri,Jerry Donovan,Jordi Barretina,Jordi Barretina,Jesse S. Boehm,Jennifer Dobson,Jennifer Dobson,Mitsuyoshi Urashima,Kevin T. Mc Henry,Reid M. Pinchback,Azra H. Ligon,Yoon Jae Cho,Leila Haery,Leila Haery,Heidi Greulich,Michael R. Reich,Wendy Winckler,Michael S. Lawrence,Barbara A. Weir,Barbara A. Weir,Kumiko E. Tanaka,Kumiko E. Tanaka,Derek Y. Chiang,Derek Y. Chiang,Derek Y. Chiang,Adam J. Bass,Adam J. Bass,Adam J. Bass,Alice Loo,Carter Hoffman,Carter Hoffman,John R. Prensner,John R. Prensner,Ted Liefeld,Qing Gao,Derek Yecies,Sabina Signoretti,Sabina Signoretti,Elizabeth A. Maher,Frederic J. Kaye,Hidefumi Sasaki,Joel E. Tepper,Jonathan A. Fletcher,Josep Tabernero,José Baselga,Ming-Sound Tsao,Francesca Demichelis,Mark A. Rubin,Pasi A. Jänne,Pasi A. Jänne,Mark J. Daly,Mark J. Daly,Carmelo Nucera,Ross L. Levine,Benjamin L. Ebert,Benjamin L. Ebert,Benjamin L. Ebert,Stacey Gabriel,Anil K. Rustgi,Cristina R. Antonescu,Marc Ladanyi,Anthony Letai,Levi A. Garraway,Levi A. Garraway,Massimo Loda,Massimo Loda,David G. Beer,Lawrence D. True,Aikou Okamoto,Scott L. Pomeroy,Samuel Singer,Todd R. Golub,Todd R. Golub,Todd R. Golub,Eric S. Lander,Eric S. Lander,Eric S. Lander,Gad Getz,William R. Sellers,Matthew Meyerson,Matthew Meyerson +86 more
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Patterns of Somatic Mutation in Human Cancer Genomes
TL;DR: In this paper, the coding exons of the family of 518 protein kinases were sequenced in 210 cancers of diverse histological types to explore the nature of the information that will be derived from cancer genome sequencing.
Journal ArticleDOI
Patterns of somatic mutation in human cancer genomes
Christopher Greenman,Philip J. Stephens,Raffaella Smith,Gillian L. Dalgliesh,Christopher I. Hunter,Graham R. Bignell,Helen Davies,Jon W. Teague,Adam Butler,Claire Stevens,Sarah Edkins,Sarah O’Meara,Imre Vastrik,Esther Schmidt,Tim Avis,Syd Barthorpe,Gurpreet Bhamra,Gemma Buck,Bhudipa Choudhury,Jody Clements,Jennifer Cole,Ed Dicks,Simon A. Forbes,Kris Gray,Kelly Halliday,Rachel Harrison,Katy Hills,Jon Hinton,Andy Jenkinson,David T. Jones,Andy Menzies,Tatiana Mironenko,Janet Perry,Keiran Raine,Dave Richardson,Rebecca Shepherd,Alexandra Small,Calli Tofts,Jennifer Varian,Tony Webb,Sofie West,Sara Widaa,Andrew D. Yates,Daniel P. Cahill,David N. Louis,Peter Goldstraw,Andrew G. Nicholson,Francis Brasseur,Leendert H. J. Looijenga,Barbara L. Weber,Yoke Eng Chiew,Anna deFazio,Mel Greaves,Anthony R. Green,Peter J. Campbell,Ewan Birney,Douglas F. Easton,Georgia Chenevix-Trench,Min-Han Tan,Sok Kean Khoo,Bin Tean Teh,Siu Tsan Yuen,Suet Yi Leung,Richard Wooster,P. Andrew Futreal,Michael R. Stratton,Michael R. Stratton +66 more
TL;DR: More than 1,000 somatic mutations found in 274 megabases of DNA corresponding to the coding exons of 518 protein kinase genes in 210 diverse human cancers reveal the evolutionary diversity of cancers and implicates a larger repertoire of cancer genes than previously anticipated.
Journal ArticleDOI
Somatic mutations affect key pathways in lung adenocarcinoma
Li Ding,Gad Getz,David A. Wheeler,Elaine R. Mardis,Michael D. McLellan,Kristian Cibulskis,Carrie Sougnez,Heidi Greulich,Heidi Greulich,Donna M. Muzny,Margaret Morgan,Lucinda Fulton,Robert S. Fulton,Qunyuan Zhang,Michael C. Wendl,Michael S. Lawrence,David E. Larson,Ken Chen,David J. Dooling,Aniko Sabo,Alicia Hawes,Hua Shen,Shalini N. Jhangiani,Lora Lewis,Otis Hall,Yiming Zhu,Tittu Mathew,Yanru Ren,Jiqiang Yao,Steven E. Scherer,Kerstin Clerc,Ginger A. Metcalf,Brian Ng,Aleksandar Milosavljevic,Manuel L. Gonzalez-Garay,John R. Osborne,Rick Meyer,Xiaoqi Shi,Yuzhu Tang,Daniel C. Koboldt,Ling Lin,Rachel Abbott,Tracie L. Miner,Craig Pohl,Ginger A. Fewell,Carrie A. Haipek,Heather Schmidt,Brian H. Dunford-Shore,Aldi T. Kraja,Seth D. Crosby,Christopher S. Sawyer,Tammi L. Vickery,Sacha N. Sander,Jody S. Robinson,Wendy Winckler,Wendy Winckler,Jennifer Baldwin,Lucian R. Chirieac,Amit Dutt,Amit Dutt,Timothy Fennell,Megan Hanna,Megan Hanna,Bruce E. Johnson,Robert C. Onofrio,Roman K. Thomas,Giovanni Tonon,Barbara A. Weir,Barbara A. Weir,Xiaojun Zhao,Xiaojun Zhao,Liuda Ziaugra,Michael C. Zody,Thomas J. Giordano,Mark B. Orringer,Jack A. Roth,Margaret R. Spitz,Ignacio I. Wistuba,Bradley A. Ozenberger,Peter J. Good,Andrew C. Chang,David G. Beer,Mark A. Watson,Marc Ladanyi,Stephen R. Broderick,Akihiko Yoshizawa,William D. Travis,William Pao,Michael A. Province,George M. Weinstock,Harold E. Varmus,Stacey Gabriel,Eric S. Lander,Richard A. Gibbs,Matthew Meyerson,Matthew Meyerson,Richard K. Wilson +96 more
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