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Abstract

Over the past decade, comprehensive sequencing efforts have revealed the genomic landscapes of common forms of human cancer. For most cancer types, this landscape consists of a small number of “mountains” (genes altered in a high percentage of tumors) and a much larger number of “hills” (genes altered infrequently). To date, these studies have revealed ~140 genes that, when altered by intragenic mutations, can promote or “drive” tumorigenesis. A typical tumor contains two to eight of these “driver gene” mutations; the remaining mutations are passengers that confer no selective growth advantage. Driver genes can be classified into 12 signaling pathways that regulate three core cellular processes: cell fate, cell survival, and genome maintenance. A better understanding of these pathways is one of the most pressing needs in basic cancer research. Even now, however, our knowledge of cancer genomes is sufficient to guide the development of more effective approaches for reducing cancer morbidity and mortality.

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Supplementary Material

Summary

Tables S1 to S5

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Science
Volume 339 | Issue 6127
29 March 2013

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Published in print: 29 March 2013

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Acknowledgments

We thank M. Nowak and I. Bozic for critical reading of the manuscript, S. Gabelli for assisting with the production of Fig. 8, and A. Dixon, V. Ferranta, and E. Cook for artwork. This work was supported by The Virginia and D.K. Ludwig Fund for Cancer Research; The Lustgarten Foundation for Pancreatic Cancer Research; and NIH grants CA 43460, CA 47345, CA 62924, and CA 121113. All authors are Founding Scientific Advisors of Personal Genome Diagnostics (PGDx), a company focused on the identification of genetic alterations in human cancer for diagnostic and therapeutic purposes. All authors are also members of the Scientific Advisory Board of Inostics, a company that is developing technologies for the molecular diagnosis of cancer. All authors own stock in PGDx and Inostics. The terms of these arrangements are being managed by Johns Hopkins University, in accordance with their conflict-of-interest policies.

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Bert Vogelstein
The Ludwig Center and The Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21287, USA.
Nickolas Papadopoulos
The Ludwig Center and The Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21287, USA.
Victor E. Velculescu
The Ludwig Center and The Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21287, USA.
Shibin Zhou
The Ludwig Center and The Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21287, USA.
Luis A. Diaz, Jr.
The Ludwig Center and The Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21287, USA.
Kenneth W. Kinzler* [email protected]
The Ludwig Center and The Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21287, USA.

Notes

*
Corresponding author. E-mail: [email protected]

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