Sensitive mutation detection in heterogeneous cancer specimens by massively parallel picoliter reactor sequencing.
The sensitivity of conventional DNA sequencing in tumor biopsies is limited by stromal contamination and by genetic heterogeneity within the cancer. Here, we show that microreactor-based pyrosequencing can detect rare cancer-associated sequence variations by independent and parallel sampling of multiple representatives of a given DNA fragment. This technology can thereby facilitate accurate molecular diagnosis of heterogeneous cancer specimens and enable patient selection for targeted cancer therapies.
Thomas
Roman K
RK
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA.
Nickerson
Elizabeth
E
Simons
Jan F
JF
Jänne
Pasi A
PA
Tengs
Torstein
T
Yuza
Yuki
Y
Garraway
Levi A
LA
LaFramboise
Thomas
T
Lee
Jeffrey C
JC
Shah
Kinjal
K
O'Neill
Keith
K
Sasaki
Hidefumi
H
Lindeman
Neal
N
Wong
Kwok-Kin
KK
Borras
Ana M
AM
Gutmann
Edward J
EJ
Dragnev
Konstantin H
KH
DeBiasi
Ralph
R
Chen
Tzu-Hsiu
TH
Glatt
Karen A
KA
Greulich
Heidi
H
Desany
Brian
B
Lubeski
Christine K
CK
Brockman
William
W
Alvarez
Pablo
P
Hutchison
Stephen K
SK
Leamon
J H
JH
Ronan
Michael T
MT
Turenchalk
Gregory S
GS
Egholm
Michael
M
Sellers
William R
WR
Rothberg
Jonathan M
JM
Meyerson
Matthew
M
D001483:Base Sequence; D002874:Chromosome Mapping / Q000379:methods*; D004273:DNA, Neoplasm / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009369:Neoplasms / Q000175:diagnosis / Q000235:genetics*; D012680:Sensitivity and Specificity
D004273:DNA, Neoplasm