A pilot study of high-throughput, sequence-based mutational profiling of primary human acute myeloid leukemia cell genomes.
In this pilot study, we used primary human acute myeloid leukemia (AML) cell genomes as templates for exonic PCR amplification, followed by high-throughput resequencing, analyzing approximately 7 million base pairs of DNA from 140 AML samples and 48 controls. We identified six previously described, and seven previously undescribed sequence changes that may be relevant for AML pathogenesis. Because the sequencing templates were generated from primary AML cells, the technique favors the detection of mutations from the most dominant clones within the tumor cell mixture. This strategy represents a viable approach for the detection of potentially relevant, nonrandom mutations in primary human cancer cell genomes.
Ley
Timothy J
TJ
Department of Medicine, Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63110, USA. tley@im.wustl.edu
Minx
Patrick J
PJ
Walter
Matthew J
MJ
Ries
Rhonda E
RE
Sun
Hui
H
McLellan
Michael
M
DiPersio
John F
JF
Link
Daniel C
DC
Tomasson
Michael H
MH
Graubert
Timothy A
TA
McLeod
Howard
H
Khoury
Hanna
H
Watson
Mark
M
Shannon
William
W
Trinkaus
Kathryn
K
Heath
Sharon
S
Vardiman
James W
JW
Caligiuri
Michael A
MA
Bloomfield
Clara D
CD
Milbrandt
Jeffrey D
JD
Mardis
Elaine R
ER
Wilson
Richard K
RK
D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D020869:Gene Expression Profiling / Q000379:methods* / Q000706:statistics & numerical data; D018095:Germ-Line Mutation; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D009154:Mutation; D010865:Pilot Projects; D012680:Sensitivity and Specificity