Systematic efforts are underway to decipher the genetic changes associated with tumor initiation and progression^{1, 2}. 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.

NOTE: In the version of this article initially published, the name of an author was spelled incorrectly as Laura MacConnaill. The correct spelling is Laura MacConaill. The error has been corrected in the HTML and PDF versions of the article.

1. Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA.
2. The Broad Institute of M.I.T. and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA.
3. Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center at Dallas, 6000 Harry Hines Boulevard, Dallas, Texas 75390-8593, USA.
4. Department of Surgery 2, Nagoya City University Medical School, Nagoya 467-8601, Japan.
5. Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
6. Departments of Internal Medicine and Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
7. Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
8. Department of Molecular and Medical Pharmacology and Medicine, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles California 90095-1732, USA.
9. Department of Pathology, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, California 90095-1732, USA.
10. Department of Neurology, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, California 90095-1732, USA.
11. Department of Human Genetics, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, California 90095-1732, USA.
12. Department of Neurosurgery, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, California 90095-1732, USA.
13. Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, Massachusetts 02115, USA.
14. Institute of Surgical Pathology, University Hospital Zürich, 8091 Zürich, Switzerland.
15. Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60637, USA.
16. Genetics Branch, Center for Cancer Research, National Cancer Institute and National Naval Medical Center, Bethesda, Maryland, USA.
17. Ludwig Center for Cancer Research at Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
18. Department of Dermatology, University Hospital Zürich, 8091 Zürich, Switzerland.
19. Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology, Medical University of Vienna, and Center of Molecular Medicine, Austrian Academy of Sciences, Wahringer Gurtel 18-20, A-1090 Vienna, Austria.
20. The Wistar Institute, 3601 Spruce Street, Philadelphia, Pennsylvania 19104, USA.
21. Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
22. Department of Pathology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
23. Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA.
24. Melanoma Program in Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA.
25. Max Planck Institute for Neurological Research with Klaus Joachim Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne, Gleueler Str. 50, 50931 Cologne, Germany.
26. Center for Integrated Oncology and Department I for Internal Medicine, University of Cologne, 50931 Cologne, Germany.
27. These authors contributed equally to this work.

Correspondence to: Levi A Garraway^1,2,23,24 e-mail: levi_garraway@dfci.harvard.edu

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