The consensus coding sequences of human breast and colorectal cancers.
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.
Sjöblom
Tobias
T
Ludwig Center and Howard Hughes Medical Institute, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231, USA.
Jones
Siân
S
Wood
Laura D
LD
Parsons
D Williams
DW
Lin
Jimmy
J
Barber
Thomas D
TD
Mandelker
Diana
D
Leary
Rebecca J
RJ
Ptak
Janine
J
Silliman
Natalie
N
Szabo
Steve
S
Buckhaults
Phillip
P
Farrell
Christopher
C
Meeh
Paul
P
Markowitz
Sanford D
SD
Willis
Joseph
J
Dawson
Dawn
D
Willson
James K V
JK
Gazdar
Adi F
AF
Hartigan
James
J
Wu
Leo
L
Liu
Changsheng
C
Parmigiani
Giovanni
G
Park
Ben Ho
BH
Bachman
Kurtis E
KE
Papadopoulos
Nickolas
N
Vogelstein
Bert
B
Kinzler
Kenneth W
KW
Velculescu
Victor E
VE
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