High-throughput oncogene mutation profiling in human cancer

Roman K. Thomas, Alissa C. Baker, Ralph M. DeBiasi, Wendy Winckler, Thomas LaFramboise, William M. Lin, Meng Wang, Whei Feng, Thomas Zander, Laura E. MacConnaill, Jeffrey C. Lee, Rick Nicoletti, Charlie Hatton, Mary Goyette, Luc Girard, Kuntal Majmudar, Liuda Ziaugra, Kwok Kin Wong, Stacey Gabriel, Rameen BeroukhimMichael Peyton, Jordi Barretina, Amit Dutt, Caroline Emery, Heidi Greulich, Kinjal Shah, Hidefumi Sasaki, Adi Gazdar, John Minna, Scott A. Armstrong, Ingo K. Mellinghoff, F. Stephen Hodi, Glenn Dranoff, Paul S. Mischel, Tim F. Cloughesy, Stan F. Nelson, Linda M. Liau, Kirsten Mertz, Mark A. Rubin, Holger Moch, Massimo Loda, William Catalona, Jonathan Fletcher, Sabina Signoretti, Frederic Kaye, Kenneth C. Anderson, George D. Demetri, Reinhard Dummer, Stephan Wagner, Meenhard Herlyn, William R. Sellers, Matthew Meyerson, Levi A. Garraway

Research output: Contribution to journalArticle

802 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)347-351
Number of pages5
JournalNature genetics
Volume39
Issue number3
DOIs
StatePublished - Mar 1 2007

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ASJC Scopus subject areas

  • Genetics

Cite this

Thomas, R. K., Baker, A. C., DeBiasi, R. M., Winckler, W., LaFramboise, T., Lin, W. M., Wang, M., Feng, W., Zander, T., MacConnaill, L. E., Lee, J. C., Nicoletti, R., Hatton, C., Goyette, M., Girard, L., Majmudar, K., Ziaugra, L., Wong, K. K., Gabriel, S., ... Garraway, L. A. (2007). High-throughput oncogene mutation profiling in human cancer. Nature genetics, 39(3), 347-351. https://doi.org/10.1038/ng1975