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Functional genomic landscape of acute myeloid leukaemia.
Tyner, Jeffrey W; Tognon, Cristina E; Bottomly, Daniel; Wilmot, Beth; Kurtz, Stephen E; Savage, Samantha L; Long, Nicola; Schultz, Anna Reister; Traer, Elie; Abel, Melissa; Agarwal, Anupriya; Blucher, Aurora; Borate, Uma; Bryant, Jade; Burke, Russell; Carlos, Amy; Carpenter, Richie; Carroll, Joseph; Chang, Bill H; Coblentz, Cody; d'Almeida, Amanda; Cook, Rachel; Danilov, Alexey; Dao, Kim-Hien T; Degnin, Michie; Devine, Deirdre; Dibb, James; Edwards, David K; Eide, Christopher A; English, Isabel; Glover, Jason; Henson, Rachel; Ho, Hibery; Jemal, Abdusebur; Johnson, Kara; Johnson, Ryan; Junio, Brian; Kaempf, Andy; Leonard, Jessica; Lin, Chenwei; Liu, Selina Qiuying; Lo, Pierrette; Loriaux, Marc M; Luty, Samuel; Macey, Tara; MacManiman, Jason; Martinez, Jacqueline; Mori, Motomi; Nelson, Dylan; Nichols, Ceilidh.
Afiliación
  • Tyner JW; Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, Portland, OR, USA.
  • Tognon CE; Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
  • Bottomly D; Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
  • Wilmot B; Division of Hematology & Medical Oncology, Department of Medicine, Oregon Health & Science University, Portland, OR, USA.
  • Kurtz SE; Howard Hughes Medical Institute, Portland, OR, USA.
  • Savage SL; Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
  • Long N; Division of Bioinformatics and Computational Biology, Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, OR, USA.
  • Schultz AR; Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
  • Traer E; Division of Bioinformatics and Computational Biology, Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, OR, USA.
  • Abel M; Oregon Clinical & Translational Research Institute, Oregon Health & Science University, Portland, OR, USA.
  • Agarwal A; Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
  • Blucher A; Division of Hematology & Medical Oncology, Department of Medicine, Oregon Health & Science University, Portland, OR, USA.
  • Borate U; Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, Portland, OR, USA.
  • Bryant J; Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
  • Burke R; Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
  • Carlos A; Division of Hematology & Medical Oncology, Department of Medicine, Oregon Health & Science University, Portland, OR, USA.
  • Carpenter R; Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, Portland, OR, USA.
  • Carroll J; Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
  • Chang BH; Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
  • Coblentz C; Division of Hematology & Medical Oncology, Department of Medicine, Oregon Health & Science University, Portland, OR, USA.
  • d'Almeida A; Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, Portland, OR, USA.
  • Cook R; Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
  • Danilov A; Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
  • Dao KT; Department of Molecular & Medical Genetics, Oregon Health & Science University, Portland, OR, USA.
  • Degnin M; Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
  • Devine D; Division of Bioinformatics and Computational Biology, Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, OR, USA.
  • Dibb J; Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
  • Edwards DK; Division of Hematology & Medical Oncology, Department of Medicine, Oregon Health & Science University, Portland, OR, USA.
  • Eide CA; Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, Portland, OR, USA.
  • English I; Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
  • Glover J; Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
  • Henson R; Division of Hematology & Medical Oncology, Department of Medicine, Oregon Health & Science University, Portland, OR, USA.
  • Ho H; Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
  • Jemal A; Integrated Genomics Laboratories, Oregon Health & Science University, Portland, OR, USA.
  • Johnson K; Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
  • Johnson R; Division of Hematology & Medical Oncology, Department of Medicine, Oregon Health & Science University, Portland, OR, USA.
  • Junio B; Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
  • Kaempf A; Technology Transfer & Business Development, Oregon Health & Science University, Portland, OR, USA.
  • Leonard J; Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
  • Lin C; Division of Hematology and Oncology, Department of Pediatrics, Oregon Health & Science University, Portland, OR, USA.
  • Liu SQ; Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
  • Lo P; Division of Hematology & Medical Oncology, Department of Medicine, Oregon Health & Science University, Portland, OR, USA.
  • Loriaux MM; Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, Portland, OR, USA.
  • Luty S; Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
  • Macey T; Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
  • MacManiman J; Division of Hematology & Medical Oncology, Department of Medicine, Oregon Health & Science University, Portland, OR, USA.
  • Martinez J; Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
  • Mori M; Division of Hematology & Medical Oncology, Department of Medicine, Oregon Health & Science University, Portland, OR, USA.
  • Nelson D; Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
  • Nichols C; Division of Hematology & Medical Oncology, Department of Medicine, Oregon Health & Science University, Portland, OR, USA.
Nature ; 562(7728): 526-531, 2018 10.
Article en En | MEDLINE | ID: mdl-30333627
ABSTRACT
The implementation of targeted therapies for acute myeloid leukaemia (AML) has been challenging because of the complex mutational patterns within and across patients as well as a dearth of pharmacologic agents for most mutational events. Here we report initial findings from the Beat AML programme on a cohort of 672 tumour specimens collected from 562 patients. We assessed these specimens using whole-exome sequencing, RNA sequencing and analyses of ex vivo drug sensitivity. Our data reveal mutational events that have not previously been detected in AML. We show that the response to drugs is associated with mutational status, including instances of drug sensitivity that are specific to combinatorial mutational events. Integration with RNA sequencing also revealed gene expression signatures, which predict a role for specific gene networks in the drug response. Collectively, we have generated a dataset-accessible through the Beat AML data viewer (Vizome)-that can be leveraged to address clinical, genomic, transcriptomic and functional analyses of the biology of AML.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Leucemia Mieloide Aguda / Regulación Neoplásica de la Expresión Génica / Genoma Humano / Genómica Tipo de estudio: Prognostic_studies Límite: Female / Humans / Male Idioma: En Revista: Nature Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Leucemia Mieloide Aguda / Regulación Neoplásica de la Expresión Génica / Genoma Humano / Genómica Tipo de estudio: Prognostic_studies Límite: Female / Humans / Male Idioma: En Revista: Nature Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos