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Nature genetics DOI:10.1038/ng1975

High-throughput oncogene mutation profiling in human cancer.

Publication TypeJournal Article
Year of Publication2007
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, Garraway, LA
JournalNature genetics
Volume39
Issue3
Pages347-51
Date Published2007/03/01
ISSN1061-4036
Abstract

Systematic 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.

URLhttp://dx.doi.org/10.1038/ng1975
DOI10.1038/ng1975
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/17293865?dopt=Abstract