High-throughput oncogene mutation profiling in human cancer.
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.
Thomas
Roman K
RK
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA.
Baker
Alissa C
AC
Debiasi
Ralph M
RM
Winckler
Wendy
W
Laframboise
Thomas
T
Lin
William M
WM
Wang
Meng
M
Feng
Whei
W
Zander
Thomas
T
MacConaill
Laura
L
Macconnaill
Laura E
LE
Lee
Jeffrey C
JC
Nicoletti
Rick
R
Hatton
Charlie
C
Goyette
Mary
M
Girard
Luc
L
Majmudar
Kuntal
K
Ziaugra
Liuda
L
Wong
Kwok-Kin
KK
Gabriel
Stacey
S
Beroukhim
Rameen
R
Peyton
Michael
M
Barretina
Jordi
J
Dutt
Amit
A
Emery
Caroline
C
Greulich
Heidi
H
Shah
Kinjal
K
Sasaki
Hidefumi
H
Gazdar
Adi
A
Minna
John
J
Armstrong
Scott A
SA
Mellinghoff
Ingo K
IK
Hodi
F Stephen
FS
Dranoff
Glenn
G
Mischel
Paul S
PS
Cloughesy
Tim F
TF
Nelson
Stan F
SF
Liau
Linda M
LM
Mertz
Kirsten
K
Rubin
Mark A
MA
Moch
Holger
H
Loda
Massimo
M
Catalona
William
W
Fletcher
Jonathan
J
Signoretti
Sabina
S
Kaye
Frederic
F
Anderson
Kenneth C
KC
Demetri
George D
GD
Dummer
Reinhard
R
Wagner
Stephan
S
Herlyn
Meenhard
M
Sellers
William R
WR
Meyerson
Matthew
M
Garraway
Levi A
LA
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