The Consensus Coding Sequences of Human Breast and Colorectal Cancers
Abstract
The elucidation of the human genome sequence has made it possible to identify genetic alterations in cancers in unprecedented detail. To begin a systematic analysis of such alterations, we determined the sequence of well-annotated human protein-coding genes in two common tumor types. Analysis of 13,023 genes in 11 breast and 11 colorectal cancers revealed that individual tumors accumulate an average of ∼90 mutant genes but that only a subset of these contribute to the neoplastic process. Using stringent criteria to delineate this subset, we identified 189 genes (average of 11 per tumor) that were mutated at significant frequency. The vast majority of these genes were not known to be genetically altered in tumors and are predicted to affect a wide range of cellular functions, including transcription, adhesion, and invasion. These data define the genetic landscape of two human cancer types, provide new targets for diagnostic and therapeutic intervention, and open fertile avenues for basic research in tumor biology.
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We thank J. Lutterbaugh, E. Lawrence, and L. Beard for assistance with cell culture and DNA preparation; E. Suh, D. Smith, K. Makowski, and the Agencourt sequencing team for assistance with automated sequencing; S. Kern for helpful comments on the manuscript; and R. J. Vogelstein and J. T. Vogelstein for assistance with statistical analyses. Supported by the Virginia and D. K. Ludwig Fund for Cancer Research; NIH grants CA 121113, CA 43460, CA 57345, CA 62924, GM 07309, RR 017698, P30-CA43703, and CA109274; NCI Division of Cancer Prevention contract HHSN261200433002C; Department of Defense grant DAMD17-03-1-0241; and the Pew Charitable Trusts, the Palmetto Health Foundation, the Maryland Cigarette Restitution Fund, the State of Ohio Biomedical Research and Technology Transfer Commission, the Clayton Fund, the Blaustein Foundation, the National Colorectal Cancer Research Alliance, the Avon Foundation, the Flight Attendant Medical Research Institute, and the V Foundation for Cancer Research.
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Science
Volume 314 | Issue 5797
13 October 2006
13 October 2006
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American Association for the Advancement of Science.
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Received: 3 August 2006
Accepted: 30 August 2006
Published in print: 13 October 2006
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