title: DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome.
abstract: 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.
authors.affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63108, USA.
authors.forename: Timothy J
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authors.forename: Elaine R
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authors.lastname: Mardis
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authors.lastname: Ding
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authors.lastname: Chen
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authors.lastname: Abbott
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authors.initials: DE
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authors.forename: Ladeana W
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authors.forename: Tracie
authors.initials: T
authors.lastname: Miner
authors.forename: Lucinda
authors.initials: L
authors.lastname: Fulton
authors.forename: Vincent
authors.initials: V
authors.lastname: Magrini
authors.forename: Todd
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authors.lastname: Wylie
authors.forename: Jarret
authors.initials: J
authors.lastname: Glasscock
authors.forename: Joshua
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authors.lastname: Sander
authors.forename: Xiaoqi
authors.initials: X
authors.lastname: Shi
authors.forename: John R
authors.initials: JR
authors.lastname: Osborne
authors.forename: Patrick
authors.initials: P
authors.lastname: Minx
authors.forename: David
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authors.lastname: Gordon
authors.forename: Asif
authors.initials: A
authors.lastname: Chinwalla
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhao
authors.forename: Rhonda E
authors.initials: RE
authors.lastname: Ries
authors.forename: Jacqueline E
authors.initials: JE
authors.lastname: Payton
authors.forename: Peter
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authors.lastname: Westervelt
authors.forename: Michael H
authors.initials: MH
authors.lastname: Tomasson
authors.forename: Mark
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authors.lastname: Watson
authors.forename: Jack
authors.initials: J
authors.lastname: Baty
authors.forename: Jennifer
authors.initials: J
authors.lastname: Ivanovich
authors.forename: Sharon
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authors.lastname: Heath
authors.forename: William D
authors.initials: WD
authors.lastname: Shannon
authors.forename: Rakesh
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authors.lastname: Nagarajan
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Walter
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Link
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Graubert
authors.forename: John F
authors.initials: JF
authors.lastname: DiPersio
authors.forename: Richard K
authors.initials: RK
authors.lastname: Wilson
mesh_terms: 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