Scientific Publications

Somatic mutations affect key pathways in lung adenocarcinoma.

Publication TypeJournal Article
AuthorsDing, L., Getz G., Wheeler DA, Mardis ER, McLellan MD, Cibulskis K., Sougnez C., Greulich H., Muzny DM, Morgan MB, Fulton L., Fulton RS, Zhang Q., Wendl MC, Lawrence MS, Larson DE, Chen K., Dooling DJ, Sabo A., Hawes AC, Shen H., Jhangiani SN, Lewis LR, Hall O., Zhu Y., Mathew T., Ren Y., Yao J., Scherer SE, Clerc K., Metcalf GA, Ng B., Milosavljevic A., Gonzalez-Garay ML, Osborne JR, Meyer R., Shi X., Tang Y., Koboldt DC, Lin L., Abbott R., Miner TL, Pohl C., Fewell G., Haipek C., Schmidt H., Dunford-Shore BH, Kraja A., Crosby SD, Sawyer CS, Vickery T., Sander S., Robinson J., Winckler W., Baldwin J., Chirieac LR, Dutt A., Fennell T., Hanna M., Johnson B. E., Onofrio RC, Thomas RK, Tonon G., Weir BA, Zhao X., Ziaugra L., Zody MC, Giordano T., Orringer MB, Roth JA, Spitz MR, Wistuba II, Ozenberger B., Good PJ, Chang AC, Beer DG, Watson MA, Ladanyi M., Broderick S., Yoshizawa A., Travis WD, Pao W., Province MA, Weinstock GM, Varmus HE, Gabriel SB, Lander E. S., Gibbs RA, Meyerson M., and Wilson RK
AbstractDetermining 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.
Year of Publication2008
JournalNature
Volume455
Issue7216
Pages1069-75
Date Published (YYYY/MM/DD)2008/10/23
ISSN Number0028-0836
DOI10.1038/nature07423
PubMedhttp://www.ncbi.nlm.nih.gov/pubmed/18948947?dopt=Abstract