DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome.
Acute myeloid leukaemia is a highly malignant haematopoietic tumour that affects about 13,000 adults in the United States each year. The treatment of this disease has changed little in the past two decades, because most of the genetic events that initiate the disease remain undiscovered. Whole-genome sequencing is now possible at a reasonable cost and timeframe to use this approach for the unbiased discovery of tumour-specific somatic mutations that alter the protein-coding genes. Here we present the results obtained from sequencing a typical acute myeloid leukaemia genome, and its matched normal counterpart obtained from the same patient's skin. We discovered ten genes with acquired mutations; two were previously described mutations that are thought to contribute to tumour progression, and eight were new mutations present in virtually all tumour cells at presentation and relapse, the function of which is not yet known. Our study establishes whole-genome sequencing as an unbiased method for discovering cancer-initiating mutations in previously unidentified genes that may respond to targeted therapies.
Ley
Timothy J
TJ
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63108, USA.
Mardis
Elaine R
ER
Ding
Li
L
Fulton
Bob
B
McLellan
Michael D
MD
Chen
Ken
K
Dooling
David
D
Dunford-Shore
Brian H
BH
McGrath
Sean
S
Hickenbotham
Matthew
M
Cook
Lisa
L
Abbott
Rachel
R
Larson
David E
DE
Koboldt
Dan C
DC
Pohl
Craig
C
Smith
Scott
S
Hawkins
Amy
A
Abbott
Scott
S
Locke
Devin
D
Hillier
Ladeana W
LW
Miner
Tracie
T
Fulton
Lucinda
L
Magrini
Vincent
V
Wylie
Todd
T
Glasscock
Jarret
J
Conyers
Joshua
J
Sander
Nathan
N
Shi
Xiaoqi
X
Osborne
John R
JR
Minx
Patrick
P
Gordon
David
D
Chinwalla
Asif
A
Zhao
Yu
Y
Ries
Rhonda E
RE
Payton
Jacqueline E
JE
Westervelt
Peter
P
Tomasson
Michael H
MH
Watson
Mark
M
Baty
Jack
J
Ivanovich
Jennifer
J
Heath
Sharon
S
Shannon
William D
WD
Nagarajan
Rakesh
R
Walter
Matthew J
MJ
Link
Daniel C
DC
Graubert
Timothy A
TA
DiPersio
John F
JF
Wilson
Richard K
RK
D016022:Case-Control Studies; D018450:Disease Progression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D015894:Genome, Human / Q000235:genetics*; D023281:Genomics; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D016254:Mutagenesis, Insertional; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D012008:Recurrence; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D012867:Skin / Q000378:metabolism