Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia.

Cancer Genome Atlas Research Network | Ley TJ | Miller C | Ding L | Raphael BJ | Mungall AJ | Robertson A | Hoadley K | Triche TJ | Laird PW | Baty JD | Fulton LL | Fulton R | Heath SE | Kalicki-Veizer J | Kandoth C | Klco JM | Koboldt DC | Kanchi KL | Kulkarni S | Lamprecht TL | Larson DE | Lin L | Lu C | McLellan MD | McMichael JF | Payton J | Schmidt H | Spencer DH | Tomasson MH | Wallis JW | Wartman LD | Watson MA | Welch J | Wendl MC | Ally A | Balasundaram M | Birol I | Butterfield Y | Chiu R | Chu A | Chuah E | Chun HJ | Corbett R | Dhalla N | Guin R | He A | Hirst C | Hirst M | Holt RA | Jones S | Karsan A | Lee D | Li HI | Marra MA | Mayo M | Moore RA | Mungall K | Parker J | Pleasance E | Plettner P | Schein J | Stoll D | Swanson L | Tam A | Thiessen N | Varhol R | Wye N | Zhao Y | Gabriel S | Getz G | Sougnez C | Zou L | Leiserson MD | Vandin F | Wu HT | Applebaum F | Baylin SB | Akbani R | Broom BM | Chen K | Motter TC | Nguyen K | Weinstein JN | Zhang N | Ferguson ML | Adams C | Black A | Bowen J | Gastier-Foster J | Grossman T | Lichtenberg T | Wise L | Davidsen T | Demchok JA | Shaw KR | Sheth M | Sofia HJ | Yang L | Downing JR | Eley G

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.).

Pubmed ID: 23634996 RIS Download

Mesh terms: Adult | CpG Islands | DNA Methylation | Epigenomics | Female | Gene Expression | Gene Fusion | Genome, Human | Humans | Leukemia, Myeloid, Acute | Male | MicroRNAs | Middle Aged | Mutation | Sequence Analysis, DNA

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

  • Agency: NCI NIH HHS, Id: U24CA143840
  • Agency: NCI NIH HHS, Id: P01CA101937
  • Agency: NCI NIH HHS, Id: P30 CA016672
  • Agency: NCI NIH HHS, Id: U24 CA143882
  • Agency: NHGRI NIH HHS, Id: U54 HG003067
  • Agency: NHGRI NIH HHS, Id: U54HG003273
  • Agency: NCI NIH HHS, Id: U24 CA143835
  • Agency: NCI NIH HHS, Id: U24 CA143866
  • Agency: NCI NIH HHS, Id: U24CA143858
  • Agency: NCI NIH HHS, Id: U24CA143882
  • Agency: NCI NIH HHS, Id: U24CA144025
  • Agency: NHGRI NIH HHS, Id: U54HG003067
  • Agency: NCI NIH HHS, Id: U24 CA143845
  • Agency: NCI NIH HHS, Id: U24 CA143799
  • Agency: NHGRI NIH HHS, Id: U54 HG003273
  • Agency: NHGRI NIH HHS, Id: R01 HG005690
  • Agency: NCI NIH HHS, Id: U24 CA144025
  • Agency: NCI NIH HHS, Id: U24CA143883
  • Agency: NHGRI NIH HHS, Id: U54HG003079
  • Agency: NCI NIH HHS, Id: U24 CA143840
  • Agency: NCI NIH HHS, Id: U24 CA143843
  • Agency: NCI NIH HHS, Id: U24CA143867
  • Agency: NCI NIH HHS, Id: U24CA143835
  • Agency: NCI NIH HHS, Id: U24 CA143858
  • Agency: NCI NIH HHS, Id: P30 CA091842
  • Agency: NCI NIH HHS, Id: U24CA143843
  • Agency: NCI NIH HHS, Id: U24 CA143848
  • Agency: NCI NIH HHS, Id: P01 CA101937
  • Agency: NCI NIH HHS, Id: U24CA143848
  • Agency: NHGRI NIH HHS, Id: U54 HG003079
  • Agency: NCI NIH HHS, Id: U24CA143799
  • Agency: NCI NIH HHS, Id: U24 CA143883
  • Agency: NCI NIH HHS, Id: R01 CA162086
  • Agency: NCI NIH HHS, Id: U24CA143866
  • Agency: NCI NIH HHS, Id: U24CA143845
  • Agency: NCI NIH HHS, Id: R01 CA083962
  • Agency: NCI NIH HHS, Id: U24 CA143867

OMIM (Data, Gene Annotation)

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

We have not found any resources mentioned in this publication.