The genomic landscapes of human breast and colorectal cancers.
Human cancer is caused by the accumulation of mutations in oncogenes and tumor suppressor genes. To catalog the genetic changes that occur during tumorigenesis, we isolated DNA from 11 breast and 11 colorectal tumors and determined the sequences of the genes in the Reference Sequence database in these samples. Based on analysis of exons representing 20,857 transcripts from 18,191 genes, we conclude that the genomic landscapes of breast and colorectal cancers are composed of a handful of commonly mutated gene "mountains" and a much larger number of gene "hills" that are mutated at low frequency. We describe statistical and bioinformatic tools that may help identify mutations with a role in tumorigenesis. These results have implications for understanding the nature and heterogeneity of human cancers and for using personal genomics for tumor diagnosis and therapy.
Wood
Laura D
LD
Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21231, USA.
Parsons
D Williams
DW
Jones
Siân
S
Lin
Jimmy
J
Sjöblom
Tobias
T
Leary
Rebecca J
RJ
Shen
Dong
D
Boca
Simina M
SM
Barber
Thomas
T
Ptak
Janine
J
Silliman
Natalie
N
Szabo
Steve
S
Dezso
Zoltan
Z
Ustyanksky
Vadim
V
Nikolskaya
Tatiana
T
Nikolsky
Yuri
Y
Karchin
Rachel
R
Wilson
Paul A
PA
Kaminker
Joshua S
JS
Zhang
Zemin
Z
Croshaw
Randal
R
Willis
Joseph
J
Dawson
Dawn
D
Shipitsin
Michail
M
Willson
James K V
JK
Sukumar
Saraswati
S
Polyak
Kornelia
K
Park
Ben Ho
BH
Pethiyagoda
Charit L
CL
Pant
P V Krishna
PV
Ballinger
Dennis G
DG
Sparks
Andrew B
AB
Hartigan
James
J
Smith
Douglas R
DR
Suh
Erick
E
Papadopoulos
Nickolas
N
Buckhaults
Phillip
P
Markowitz
Sanford D
SD
Parmigiani
Giovanni
G
Kinzler
Kenneth W
KW
Velculescu
Victor E
VE
Vogelstein
Bert
B
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D002874:Chromosome Mapping; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D019295:Computational Biology; D004273:DNA, Neoplasm; D030541:Databases, Genetic; D052138:Genes, Neoplasm; D015894:Genome, Human; D006801:Humans; D053858:Metabolic Networks and Pathways / Q000235:genetics; D051379:Mice; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA
D004273:DNA, Neoplasm; D009363:Neoplasm Proteins