title: Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia.
abstract: Many mutations that contribute to the pathogenesis of acute myeloid leukemia (AML) are undefined. The relationships between patterns of mutations and epigenetic phenotypes are not yet clear.
  
  
  
  We analyzed the genomes of 200 clinically annotated adult cases of de novo AML, using either whole-genome sequencing (50 cases) or whole-exome sequencing (150 cases), along with RNA and microRNA sequencing and DNA-methylation analysis.
  
  
  
  AML genomes have fewer mutations than most other adult cancers, with an average of only 13 mutations found in genes. Of these, an average of 5 are in genes that are recurrently mutated in AML. A total of 23 genes were significantly mutated, and another 237 were mutated in two or more samples. Nearly all samples had at least 1 nonsynonymous mutation in one of nine categories of genes that are almost certainly relevant for pathogenesis, including transcription-factor fusions (18% of cases), the gene encoding nucleophosmin (NPM1) (27%), tumor-suppressor genes (16%), DNA-methylation-related genes (44%), signaling genes (59%), chromatin-modifying genes (30%), myeloid transcription-factor genes (22%), cohesin-complex genes (13%), and spliceosome-complex genes (14%). Patterns of cooperation and mutual exclusivity suggested strong biologic relationships among several of the genes and categories.
  
  
  
  We identified at least one potential driver mutation in nearly all AML samples and found that a complex interplay of genetic events contributes to AML pathogenesis in individual patients. The databases from this study are widely available to serve as a foundation for further investigations of AML pathogenesis, classification, and risk stratification. (Funded by the National Institutes of Health.).
authors: Timothy J
authors: TJ
authors: Ley
authors: Christopher
authors: C
authors: Miller
authors: Li
authors: L
authors: Ding
authors: Benjamin J
authors: BJ
authors: Raphael
authors: Andrew J
authors: AJ
authors: Mungall
authors: A  Gordon
authors: A
authors: Robertson
authors: Katherine
authors: K
authors: Hoadley
authors: Timothy J
authors: TJ
authors: Triche
authors: Peter W
authors: PW
authors: Laird
authors: Jack D
authors: JD
authors: Baty
authors: Lucinda L
authors: LL
authors: Fulton
authors: Robert
authors: R
authors: Fulton
authors: Sharon E
authors: SE
authors: Heath
authors: Joelle
authors: J
authors: Kalicki-Veizer
authors: Cyriac
authors: C
authors: Kandoth
authors: Jeffery M
authors: JM
authors: Klco
authors: Daniel C
authors: DC
authors: Koboldt
authors: Krishna-Latha
authors: KL
authors: Kanchi
authors: Shashikant
authors: S
authors: Kulkarni
authors: Tamara L
authors: TL
authors: Lamprecht
authors: David E
authors: DE
authors: Larson
authors: Ling
authors: L
authors: Lin
authors: Charles
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authors: Lu
authors: Michael D
authors: MD
authors: McLellan
authors: Joshua F
authors: JF
authors: McMichael
authors: Jacqueline
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authors: Payton
authors: Heather
authors: H
authors: Schmidt
authors: David H
authors: DH
authors: Spencer
authors: Michael H
authors: MH
authors: Tomasson
authors: John W
authors: JW
authors: Wallis
authors: Lukas D
authors: LD
authors: Wartman
authors: Mark A
authors: MA
authors: Watson
authors: John
authors: J
authors: Welch
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authors: MC
authors: Wendl
authors: Adrian
authors: A
authors: Ally
authors: Miruna
authors: M
authors: Balasundaram
authors: Inanc
authors: I
authors: Birol
authors: Yaron
authors: Y
authors: Butterfield
authors: Readman
authors: R
authors: Chiu
authors: Andy
authors: A
authors: Chu
authors: Eric
authors: E
authors: Chuah
authors: Hye-Jung
authors: HJ
authors: Chun
authors: Richard
authors: R
authors: Corbett
authors: Noreen
authors: N
authors: Dhalla
authors: Ranabir
authors: R
authors: Guin
authors: An
authors: A
authors: He
authors: Carrie
authors: C
authors: Hirst
authors: Martin
authors: M
authors: Hirst
authors: Robert A
authors: RA
authors: Holt
authors: Steven
authors: S
authors: Jones
authors: Aly
authors: A
authors: Karsan
authors: Darlene
authors: D
authors: Lee
authors: Haiyan I
authors: HI
authors: Li
authors: Marco A
authors: MA
authors: Marra
authors: Michael
authors: M
authors: Mayo
authors: Richard A
authors: RA
authors: Moore
authors: Karen
authors: K
authors: Mungall
authors: Jeremy
authors: J
authors: Parker
authors: Erin
authors: E
authors: Pleasance
authors: Patrick
authors: P
authors: Plettner
authors: Jacquie
authors: J
authors: Schein
authors: Dominik
authors: D
authors: Stoll
authors: Lucas
authors: L
authors: Swanson
authors: Angela
authors: A
authors: Tam
authors: Nina
authors: N
authors: Thiessen
authors: Richard
authors: R
authors: Varhol
authors: Natasja
authors: N
authors: Wye
authors: Yongjun
authors: Y
authors: Zhao
authors: Stacey
authors: S
authors: Gabriel
authors: Gad
authors: G
authors: Getz
authors: Carrie
authors: C
authors: Sougnez
authors: Lihua
authors: L
authors: Zou
authors: Mark D M
authors: MD
authors: Leiserson
authors: Fabio
authors: F
authors: Vandin
authors: Hsin-Ta
authors: HT
authors: Wu
authors: Frederick
authors: F
authors: Applebaum
authors: Stephen B
authors: SB
authors: Baylin
authors: Rehan
authors: R
authors: Akbani
authors: Bradley M
authors: BM
authors: Broom
authors: Ken
authors: K
authors: Chen
authors: Thomas C
authors: TC
authors: Motter
authors: Khanh
authors: K
authors: Nguyen
authors: John N
authors: JN
authors: Weinstein
authors: Nianziang
authors: N
authors: Zhang
authors: Martin L
authors: ML
authors: Ferguson
authors: Christopher
authors: C
authors: Adams
authors: Aaron
authors: A
authors: Black
authors: Jay
authors: J
authors: Bowen
authors: Julie
authors: J
authors: Gastier-Foster
authors: Thomas
authors: T
authors: Grossman
authors: Tara
authors: T
authors: Lichtenberg
authors: Lisa
authors: L
authors: Wise
authors: Tanja
authors: T
authors: Davidsen
authors: John A
authors: JA
authors: Demchok
authors: Kenna R  Mills
authors: KR
authors: Shaw
authors: Margi
authors: M
authors: Sheth
authors: Heidi J
authors: HJ
authors: Sofia
authors: Liming
authors: L
authors: Yang
authors: James R
authors: JR
authors: Downing
authors: Greg
authors: G
authors: Eley
mesh_terms: D000328:Adult; D018899:CpG Islands; D019175:DNA Methylation; D057890:Epigenomics; D005260:Female; D015870:Gene Expression; D050939:Gene Fusion; D015894:Genome, Human; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000145:classification / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D000090243:Nucleophosmin; D017422:Sequence Analysis, DNA / Q000379:methods
chemical_list: D035683:MicroRNAs; C000716967:NPM1 protein, human; D000090243:Nucleophosmin
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