title: The genomic landscapes of human breast and colorectal cancers.
abstract: 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.
authors.affiliation: Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21231, USA.
authors.forename: Laura D
authors.initials: LD
authors.lastname: Wood
authors.forename: D Williams
authors.initials: DW
authors.lastname: Parsons
authors.forename: Siân
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authors.lastname: Jones
authors.forename: Jimmy
authors.initials: J
authors.lastname: Lin
authors.forename: Tobias
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authors.lastname: Sjöblom
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Leary
authors.forename: Dong
authors.initials: D
authors.lastname: Shen
authors.forename: Simina M
authors.initials: SM
authors.lastname: Boca
authors.forename: Thomas
authors.initials: T
authors.lastname: Barber
authors.forename: Janine
authors.initials: J
authors.lastname: Ptak
authors.forename: Natalie
authors.initials: N
authors.lastname: Silliman
authors.forename: Steve
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authors.lastname: Szabo
authors.forename: Zoltan
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authors.lastname: Dezso
authors.forename: Vadim
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authors.lastname: Ustyanksky
authors.forename: Tatiana
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authors.lastname: Nikolskaya
authors.forename: Yuri
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authors.lastname: Nikolsky
authors.forename: Rachel
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authors.lastname: Karchin
authors.forename: Paul A
authors.initials: PA
authors.lastname: Wilson
authors.forename: Joshua S
authors.initials: JS
authors.lastname: Kaminker
authors.forename: Zemin
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authors.lastname: Zhang
authors.forename: Randal
authors.initials: R
authors.lastname: Croshaw
authors.forename: Joseph
authors.initials: J
authors.lastname: Willis
authors.forename: Dawn
authors.initials: D
authors.lastname: Dawson
authors.forename: Michail
authors.initials: M
authors.lastname: Shipitsin
authors.forename: James K V
authors.initials: JK
authors.lastname: Willson
authors.forename: Saraswati
authors.initials: S
authors.lastname: Sukumar
authors.forename: Kornelia
authors.initials: K
authors.lastname: Polyak
authors.forename: Ben Ho
authors.initials: BH
authors.lastname: Park
authors.forename: Charit L
authors.initials: CL
authors.lastname: Pethiyagoda
authors.forename: P V Krishna
authors.initials: PV
authors.lastname: Pant
authors.forename: Dennis G
authors.initials: DG
authors.lastname: Ballinger
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Sparks
authors.forename: James
authors.initials: J
authors.lastname: Hartigan
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Smith
authors.forename: Erick
authors.initials: E
authors.lastname: Suh
authors.forename: Nickolas
authors.initials: N
authors.lastname: Papadopoulos
authors.forename: Phillip
authors.initials: P
authors.lastname: Buckhaults
authors.forename: Sanford D
authors.initials: SD
authors.lastname: Markowitz
authors.forename: Giovanni
authors.initials: G
authors.lastname: Parmigiani
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Kinzler
authors.forename: Victor E
authors.initials: VE
authors.lastname: Velculescu
authors.forename: Bert
authors.initials: B
authors.lastname: Vogelstein
mesh_terms: 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
chemical_list: D004273:DNA, Neoplasm; D009363:Neoplasm Proteins