Journal
SCIENCE
Volume 314, Issue 5797, Pages 268-274Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1133427
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Funding
- NCI NIH HHS [CA109274, CA 62924, P30-CA43703, CA 121113, CA 43460, CA 57345] Funding Source: Medline
- NCRR NIH HHS [RR 017698] Funding Source: Medline
- NIGMS NIH HHS [GM 07309] Funding Source: Medline
- PHS HHS [HHSN261200433002C] Funding Source: Medline
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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 similar to 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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