Publication Date:
2006-09-09
Description:
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 approximately 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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sjoblom, Tobias -- Jones, Sian -- Wood, Laura D -- Parsons, D Williams -- Lin, Jimmy -- Barber, Thomas D -- Mandelker, Diana -- Leary, Rebecca J -- Ptak, Janine -- Silliman, Natalie -- Szabo, Steve -- Buckhaults, Phillip -- Farrell, Christopher -- Meeh, Paul -- Markowitz, Sanford D -- Willis, Joseph -- Dawson, Dawn -- Willson, James K V -- Gazdar, Adi F -- Hartigan, James -- Wu, Leo -- Liu, Changsheng -- Parmigiani, Giovanni -- Park, Ben Ho -- Bachman, Kurtis E -- Papadopoulos, Nickolas -- Vogelstein, Bert -- Kinzler, Kenneth W -- Velculescu, Victor E -- CA 121113/CA/NCI NIH HHS/ -- CA 43460/CA/NCI NIH HHS/ -- CA 57345/CA/NCI NIH HHS/ -- CA 62924/CA/NCI NIH HHS/ -- CA109274/CA/NCI NIH HHS/ -- GM 07309/GM/NIGMS NIH HHS/ -- HHSN261200433002C/PHS HHS/ -- P30-CA43703/CA/NCI NIH HHS/ -- RR 017698/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2006 Oct 13;314(5797):268-74. Epub 2006 Sep 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ludwig Center and Howard Hughes Medical Institute, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16959974" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acid Substitution
;
Breast Neoplasms/*genetics
;
Cell Line, Tumor
;
Colorectal Neoplasms/*genetics
;
Computational Biology
;
*Consensus Sequence
;
Databases, Nucleic Acid
;
Female
;
*Genes, Neoplasm
;
Genome, Human
;
Humans
;
Male
;
*Mutation
;
Polymerase Chain Reaction
;
Sequence Analysis, DNA
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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