title: High-throughput oncogene mutation profiling in human cancer.
abstract: Systematic efforts are underway to decipher the genetic changes associated with tumor initiation and progression. However, widespread clinical application of this information is hampered by an inability to identify critical genetic events across the spectrum of human tumors with adequate sensitivity and scalability. Here, we have adapted high-throughput genotyping to query 238 known oncogene mutations across 1,000 human tumor samples. This approach established robust mutation distributions spanning 17 cancer types. Of 17 oncogenes analyzed, we found 14 to be mutated at least once, and 298 (30%) samples carried at least one mutation. Moreover, we identified previously unrecognized oncogene mutations in several tumor types and observed an unexpectedly high number of co-occurring mutations. These results offer a new dimension in tumor genetics, where mutations involving multiple cancer genes may be interrogated simultaneously and in 'real time' to guide cancer classification and rational therapeutic intervention.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA.
authors.forename: Roman K
authors.initials: RK
authors.lastname: Thomas
authors.forename: Alissa C
authors.initials: AC
authors.lastname: Baker
authors.forename: Ralph M
authors.initials: RM
authors.lastname: Debiasi
authors.forename: Wendy
authors.initials: W
authors.lastname: Winckler
authors.forename: Thomas
authors.initials: T
authors.lastname: Laframboise
authors.forename: William M
authors.initials: WM
authors.lastname: Lin
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.forename: Whei
authors.initials: W
authors.lastname: Feng
authors.forename: Thomas
authors.initials: T
authors.lastname: Zander
authors.forename: Laura
authors.initials: L
authors.lastname: MacConaill
authors.forename: Laura E
authors.initials: LE
authors.lastname: Macconnaill
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Lee
authors.forename: Rick
authors.initials: R
authors.lastname: Nicoletti
authors.forename: Charlie
authors.initials: C
authors.lastname: Hatton
authors.forename: Mary
authors.initials: M
authors.lastname: Goyette
authors.forename: Luc
authors.initials: L
authors.lastname: Girard
authors.forename: Kuntal
authors.initials: K
authors.lastname: Majmudar
authors.forename: Liuda
authors.initials: L
authors.lastname: Ziaugra
authors.forename: Kwok-Kin
authors.initials: KK
authors.lastname: Wong
authors.forename: Stacey
authors.initials: S
authors.lastname: Gabriel
authors.forename: Rameen
authors.initials: R
authors.lastname: Beroukhim
authors.forename: Michael
authors.initials: M
authors.lastname: Peyton
authors.forename: Jordi
authors.initials: J
authors.lastname: Barretina
authors.forename: Amit
authors.initials: A
authors.lastname: Dutt
authors.forename: Caroline
authors.initials: C
authors.lastname: Emery
authors.forename: Heidi
authors.initials: H
authors.lastname: Greulich
authors.forename: Kinjal
authors.initials: K
authors.lastname: Shah
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Sasaki
authors.forename: Adi
authors.initials: A
authors.lastname: Gazdar
authors.forename: John
authors.initials: J
authors.lastname: Minna
authors.forename: Scott A
authors.initials: SA
authors.lastname: Armstrong
authors.forename: Ingo K
authors.initials: IK
authors.lastname: Mellinghoff
authors.forename: F Stephen
authors.initials: FS
authors.lastname: Hodi
authors.forename: Glenn
authors.initials: G
authors.lastname: Dranoff
authors.forename: Paul S
authors.initials: PS
authors.lastname: Mischel
authors.forename: Tim F
authors.initials: TF
authors.lastname: Cloughesy
authors.forename: Stan F
authors.initials: SF
authors.lastname: Nelson
authors.forename: Linda M
authors.initials: LM
authors.lastname: Liau
authors.forename: Kirsten
authors.initials: K
authors.lastname: Mertz
authors.forename: Mark A
authors.initials: MA
authors.lastname: Rubin
authors.forename: Holger
authors.initials: H
authors.lastname: Moch
authors.forename: Massimo
authors.initials: M
authors.lastname: Loda
authors.forename: William
authors.initials: W
authors.lastname: Catalona
authors.forename: Jonathan
authors.initials: J
authors.lastname: Fletcher
authors.forename: Sabina
authors.initials: S
authors.lastname: Signoretti
authors.forename: Frederic
authors.initials: F
authors.lastname: Kaye
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Anderson
authors.forename: George D
authors.initials: GD
authors.lastname: Demetri
authors.forename: Reinhard
authors.initials: R
authors.lastname: Dummer
authors.forename: Stephan
authors.initials: S
authors.lastname: Wagner
authors.forename: Meenhard
authors.initials: M
authors.lastname: Herlyn
authors.forename: William R
authors.initials: WR
authors.lastname: Sellers
authors.forename: Matthew
authors.initials: M
authors.lastname: Meyerson
authors.forename: Levi A
authors.initials: LA
authors.lastname: Garraway
mesh_terms: D004252:DNA Mutational Analysis / Q000379:methods*; D020869:Gene Expression Profiling; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D009857:Oncogenes