title: Recurring mutations found by sequencing an acute myeloid leukemia genome.
abstract: BACKGROUND
  The full complement of DNA mutations that are responsible for the pathogenesis of acute myeloid leukemia (AML) is not yet known.
  
  
  METHODS
  We used massively parallel DNA sequencing to obtain a very high level of coverage (approximately 98%) of a primary, cytogenetically normal, de novo genome for AML with minimal maturation (AML-M1) and a matched normal skin genome.
  
  
  RESULTS
  We identified 12 acquired (somatic) mutations within the coding sequences of genes and 52 somatic point mutations in conserved or regulatory portions of the genome. All mutations appeared to be heterozygous and present in nearly all cells in the tumor sample. Four of the 64 mutations occurred in at least 1 additional AML sample in 188 samples that were tested. Mutations in NRAS and NPM1 had been identified previously in patients with AML, but two other mutations had not been identified. One of these mutations, in the IDH1 gene, was present in 15 of 187 additional AML genomes tested and was strongly associated with normal cytogenetic status; it was present in 13 of 80 cytogenetically normal samples (16%). The other was a nongenic mutation in a genomic region with regulatory potential and conservation in higher mammals; we detected it in one additional AML tumor. The AML genome that we sequenced contains approximately 750 point mutations, of which only a small fraction are likely to be relevant to pathogenesis.
  
  
  CONCLUSIONS
  By comparing the sequences of tumor and skin genomes of a patient with AML-M1, we have identified recurring mutations that may be relevant for pathogenesis.
authors: Department of Genetics, Washington University, St. Louis, MO 63110, USA.
authors: Elaine R
authors: ER
authors: Mardis
authors: Li
authors: L
authors: Ding
authors: David J
authors: DJ
authors: Dooling
authors: David E
authors: DE
authors: Larson
authors: Michael D
authors: MD
authors: McLellan
authors: Ken
authors: K
authors: Chen
authors: Daniel C
authors: DC
authors: Koboldt
authors: Robert S
authors: RS
authors: Fulton
authors: Kim D
authors: KD
authors: Delehaunty
authors: Sean D
authors: SD
authors: McGrath
authors: Lucinda A
authors: LA
authors: Fulton
authors: Devin P
authors: DP
authors: Locke
authors: Vincent J
authors: VJ
authors: Magrini
authors: Rachel M
authors: RM
authors: Abbott
authors: Tammi L
authors: TL
authors: Vickery
authors: Jerry S
authors: JS
authors: Reed
authors: Jody S
authors: JS
authors: Robinson
authors: Todd
authors: T
authors: Wylie
authors: Scott M
authors: SM
authors: Smith
authors: Lynn
authors: L
authors: Carmichael
authors: James M
authors: JM
authors: Eldred
authors: Christopher C
authors: CC
authors: Harris
authors: Jason
authors: J
authors: Walker
authors: Joshua B
authors: JB
authors: Peck
authors: Feiyu
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authors: Du
authors: Adam F
authors: AF
authors: Dukes
authors: Gabriel E
authors: GE
authors: Sanderson
authors: Anthony M
authors: AM
authors: Brummett
authors: Eric
authors: E
authors: Clark
authors: Joshua F
authors: JF
authors: McMichael
authors: Rick J
authors: RJ
authors: Meyer
authors: Jonathan K
authors: JK
authors: Schindler
authors: Craig S
authors: CS
authors: Pohl
authors: John W
authors: JW
authors: Wallis
authors: Xiaoqi
authors: X
authors: Shi
authors: Ling
authors: L
authors: Lin
authors: Heather
authors: H
authors: Schmidt
authors: Yuzhu
authors: Y
authors: Tang
authors: Carrie
authors: C
authors: Haipek
authors: Madeline E
authors: ME
authors: Wiechert
authors: Jolynda V
authors: JV
authors: Ivy
authors: Joelle
authors: J
authors: Kalicki
authors: Glendoria
authors: G
authors: Elliott
authors: Rhonda E
authors: RE
authors: Ries
authors: Jacqueline E
authors: JE
authors: Payton
authors: Peter
authors: P
authors: Westervelt
authors: Michael H
authors: MH
authors: Tomasson
authors: Mark A
authors: MA
authors: Watson
authors: Jack
authors: J
authors: Baty
authors: Sharon
authors: S
authors: Heath
authors: William D
authors: WD
authors: Shannon
authors: Rakesh
authors: R
authors: Nagarajan
authors: Daniel C
authors: DC
authors: Link
authors: Matthew J
authors: MJ
authors: Walter
authors: Timothy A
authors: TA
authors: Graubert
authors: John F
authors: JF
authors: DiPersio
authors: Richard K
authors: RK
authors: Wilson
authors: Timothy J
authors: TJ
authors: Ley
mesh_terms: D000328:Adult; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D015894:Genome, Human; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D000090243:Nucleophosmin; D017354:Point Mutation; D017422:Sequence Analysis, DNA / Q000379:methods
chemical_list: C000716967:NPM1 protein, human; D000090243:Nucleophosmin; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human