Scientific Publications

High-throughput oncogene mutation profiling in human cancer.

Publication TypeJournal Article
AuthorsThomas, RK, Baker AC, Debiasi RM, Winckler W., LaFramboise T., Lin WM, Wang M., Feng W., Zander T., MacConaill L., Lee JC, Nicoletti R., Hatton C., Goyette M., Girard L., Majmudar K., Ziaugra L., Wong KK, Gabriel S., Beroukhim R., Peyton M., Barretina J., Dutt A., Emery C., Greulich H., Shah K., Sasaki H., Gazdar A., Minna J., Armstrong SA, Mellinghoff IK, Hodi FS, Dranoff G., Mischel PS, Cloughesy TF, Nelson SF, Liau LM, Mertz K., Rubin MA, Moch H., Loda M., Catalona W., Fletcher J., Signoretti S., Kaye F., Anderson KC, Demetri GD, Dummer R., Wagner S., Herlyn M., Sellers WR, Meyerson M., and Garraway LA
AbstractSystematic efforts are underway to decipher the genetic changes associated with tumor initiation and progression. However, widespread clinical application of this information is hampered by an inability to identify critical genetic events across the spectrum of human tumors with adequate sensitivity and scalability. Here, we have adapted high-throughput genotyping to query 238 known oncogene mutations across 1,000 human tumor samples. This approach established robust mutation distributions spanning 17 cancer types. Of 17 oncogenes analyzed, we found 14 to be mutated at least once, and 298 (30%) samples carried at least one mutation. Moreover, we identified previously unrecognized oncogene mutations in several tumor types and observed an unexpectedly high number of co-occurring mutations. These results offer a new dimension in tumor genetics, where mutations involving multiple cancer genes may be interrogated simultaneously and in 'real time' to guide cancer classification and rational therapeutic intervention.
Year of Publication2007
JournalNature genetics
Volume39
Issue3
Pages347-51
Date Published (YYYY/MM/DD)2007/03/01
ISSN Number1061-4036
DOI10.1038/ng1975
PubMedhttp://www.ncbi.nlm.nih.gov/pubmed/17293865?dopt=Abstract