DOI: 10.1038/nature07423

¤ OpenAccess: Bronze

This work has “Bronze” OA status. This means it is free to read on the publisher landing page, but without any identifiable license.

Somatic mutations affect key pathways in lung adenocarcinoma

Ding Li,Gad Getz,David A. Wheeler,Elaine R. Mardis,Michael D. McLellan,Kristian Cibulskis,Carrie Sougnez,Heidi Greulich,Donna M. Muzny,Margaret Morgan,Lucinda L. 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,Yiping Zhu,Tittu Mathew,Yanru Ren,Jiqiang Yao,Steven E. Scherer,Kerstin Clerc,Ginger Metcalf,B. D. J. ng,Aleksandar Milosavljevic,Manuel L. Gonzalez-Garay,John R. Osborne,Rick Meyer,Xiaoqi Shi,Yuzhu Tang,Daniel C. Koboldt,Gang Li,Rachel M. 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,Jennifer Baldwin,Lucian R. Chirieac,Amit Dutt,Tim Fennell,Megan Hanna,Bruce E. Johnson,Robert C. Onofrio,Roman K. Thomas,Giovanni Tonon,Barbara A. Weir,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 Broderick,Akihiko Yoshizawa,William D. Travis,William Pao,Michael A. Province,George M. Weinstock,Harold Varmus,Stacey Gabriel,Eric S. Lander,Richard A. Gibbs,Matthew Meyerson,Richard K. Wilson

Biology

Somatic cell

Gene

2008

Determining the genetic basis of cancer requires comprehensive analyses of large collections of histopathologically well-classified primary tumours. Here we report the results of a collaborative study to discover somatic mutations in 188 human lung adenocarcinomas. DNA sequencing of 623 genes with known or potential relationships to cancer revealed more than 1,000 somatic mutations across the samples. Our analysis identified 26 genes that are mutated at significantly high frequencies and thus are probably involved in carcinogenesis. The frequently mutated genes include tyrosine kinases, among them the EGFR homologue ERBB4; multiple ephrin receptor genes, notably EPHA3; vascular endothelial growth factor receptor KDR; and NTRK genes. These data provide evidence of somatic mutations in primary lung adenocarcinoma for several tumour suppressor genes involved in other cancers--including NF1, APC, RB1 and ATM--and for sequence changes in PTPRD as well as the frequently deleted gene LRP1B. The observed mutational profiles correlate with clinical features, smoking status and DNA repair defects. These results are reinforced by data integration including single nucleotide polymorphism array and gene expression array. Our findings shed further light on several important signalling pathways involved in lung adenocarcinoma, and suggest new molecular targets for treatment.

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“Somatic mutations affect key pathways in lung adenocarcinoma” is a paper by Ding Li Gad Getz David A. Wheeler Elaine R. Mardis Michael D. McLellan Kristian Cibulskis Carrie Sougnez Heidi Greulich Donna M. Muzny Margaret Morgan Lucinda L. 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 Yiping Zhu Tittu Mathew Yanru Ren Jiqiang Yao Steven E. Scherer Kerstin Clerc Ginger Metcalf B. D. J. ng Aleksandar Milosavljevic Manuel L. Gonzalez-Garay John R. Osborne Rick Meyer Xiaoqi Shi Yuzhu Tang Daniel C. Koboldt Gang Li Rachel M. 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 Jennifer Baldwin Lucian R. Chirieac Amit Dutt Tim Fennell Megan Hanna Bruce E. Johnson Robert C. Onofrio Roman K. Thomas Giovanni Tonon Barbara A. Weir 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 Broderick Akihiko Yoshizawa William D. Travis William Pao Michael A. Province George M. Weinstock Harold Varmus Stacey Gabriel Eric S. Lander Richard A. Gibbs Matthew Meyerson Richard K. Wilson published in 2008. It has an Open Access status of “bronze”. You can read and download a PDF Full Text of this paper here.