title: 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 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.
authors.affiliation: Ludwig Center and Howard Hughes Medical Institute, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231, USA.
authors.forename: Tobias
authors.initials: T
authors.lastname: Sjöblom
authors.forename: Siân
authors.initials: S
authors.lastname: Jones
authors.forename: Laura D
authors.initials: LD
authors.lastname: Wood
authors.forename: D Williams
authors.initials: DW
authors.lastname: Parsons
authors.forename: Jimmy
authors.initials: J
authors.lastname: Lin
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Barber
authors.forename: Diana
authors.initials: D
authors.lastname: Mandelker
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Leary
authors.forename: Janine
authors.initials: J
authors.lastname: Ptak
authors.forename: Natalie
authors.initials: N
authors.lastname: Silliman
authors.forename: Steve
authors.initials: S
authors.lastname: Szabo
authors.forename: Phillip
authors.initials: P
authors.lastname: Buckhaults
authors.forename: Christopher
authors.initials: C
authors.lastname: Farrell
authors.forename: Paul
authors.initials: P
authors.lastname: Meeh
authors.forename: Sanford D
authors.initials: SD
authors.lastname: Markowitz
authors.forename: Joseph
authors.initials: J
authors.lastname: Willis
authors.forename: Dawn
authors.initials: D
authors.lastname: Dawson
authors.forename: James K V
authors.initials: JK
authors.lastname: Willson
authors.forename: Adi F
authors.initials: AF
authors.lastname: Gazdar
authors.forename: James
authors.initials: J
authors.lastname: Hartigan
authors.forename: Leo
authors.initials: L
authors.lastname: Wu
authors.forename: Changsheng
authors.initials: C
authors.lastname: Liu
authors.forename: Giovanni
authors.initials: G
authors.lastname: Parmigiani
authors.forename: Ben Ho
authors.initials: BH
authors.lastname: Park
authors.forename: Kurtis E
authors.initials: KE
authors.lastname: Bachman
authors.forename: Nickolas
authors.initials: N
authors.lastname: Papadopoulos
authors.forename: Bert
authors.initials: B
authors.lastname: Vogelstein
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Kinzler
authors.forename: Victor E
authors.initials: VE
authors.lastname: Velculescu
mesh_terms: D019943:Amino Acid Substitution; D001943:Breast Neoplasms / Q000235:genetics*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics*; D019295:Computational Biology; D016384:Consensus Sequence; D030561:Databases, Nucleic Acid; D005260:Female; D052138:Genes, Neoplasm; D015894:Genome, Human; D006801:Humans; D008297:Male; D009154:Mutation; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA