Title | High-throughput oncogene mutation profiling in human cancer. |
Publication Type | Journal Article |
Year of Publication | 2007 |
Authors | Thomas RK, Baker AC, Debiasi RM, Winckler W, Laframboise T, Lin WM, Wang M, Feng W, Zander T, MacConaill L, Macconnaill LE, Lee JC, Nicoletti R, Hatton C, Goyette M, Girard L, Majmudar K, Ziaugra L, Wong K-K, 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, F Hodi S, 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 |
Journal | Nat Genet |
Volume | 39 |
Issue | 3 |
Pagination | 347-51 |
Date Published | 2007 Mar |
ISSN | 1061-4036 |
Keywords | DNA Mutational Analysis, Gene Expression Profiling, Genome, Human, Genotype, Humans, Mutation, Neoplasms, Oncogenes |
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. |
DOI | 10.1038/ng1975 |
Alternate Journal | Nat Genet |
PubMed ID | 17293865 |
Grant List | P50 CA070907 / CA / NCI NIH HHS / United States P50CA70907 / CA / NCI NIH HHS / United States |
Related Faculty:
Massimo Loda, M.D.