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Genetic and Functional Drivers of Diffuse Large B Cell Lymphoma.
Reddy, Anupama; Zhang, Jenny; Davis, Nicholas S; Moffitt, Andrea B; Love, Cassandra L; Waldrop, Alexander; Leppa, Sirpa; Pasanen, Annika; Meriranta, Leo; Karjalainen-Lindsberg, Marja-Liisa; Nørgaard, Peter; Pedersen, Mette; Gang, Anne O; Høgdall, Estrid; Heavican, Tayla B; Lone, Waseem; Iqbal, Javeed; Qin, Qiu; Li, Guojie; Kim, So Young; Healy, Jane; Richards, Kristy L; Fedoriw, Yuri; Bernal-Mizrachi, Leon; Koff, Jean L; Staton, Ashley D; Flowers, Christopher R; Paltiel, Ora; Goldschmidt, Neta; Calaminici, Maria; Clear, Andrew; Gribben, John; Nguyen, Evelyn; Czader, Magdalena B; Ondrejka, Sarah L; Collie, Angela; Hsi, Eric D; Tse, Eric; Au-Yeung, Rex K H; Kwong, Yok-Lam; Srivastava, Gopesh; Choi, William W L; Evens, Andrew M; Pilichowska, Monika; Sengar, Manju; Reddy, Nishitha; Li, Shaoying; Chadburn, Amy; Gordon, Leo I; Jaffe, Elaine S.
Afiliación
  • Reddy A; Duke Cancer Institute and Center for Genomic and Computational Biology, Duke University, Durham, NC, USA; Department of Medicine, Duke University Medical Center, Durham, NC, USA.
  • Zhang J; Duke Cancer Institute and Center for Genomic and Computational Biology, Duke University, Durham, NC, USA; Department of Medicine, Duke University Medical Center, Durham, NC, USA.
  • Davis NS; Duke Cancer Institute and Center for Genomic and Computational Biology, Duke University, Durham, NC, USA.
  • Moffitt AB; Duke Cancer Institute and Center for Genomic and Computational Biology, Duke University, Durham, NC, USA.
  • Love CL; Duke Cancer Institute and Center for Genomic and Computational Biology, Duke University, Durham, NC, USA.
  • Waldrop A; Duke Cancer Institute and Center for Genomic and Computational Biology, Duke University, Durham, NC, USA.
  • Leppa S; Helsinki University Hospital Cancer Center and University of Helsinki, Helsinki, Finland.
  • Pasanen A; Helsinki University Hospital Cancer Center and University of Helsinki, Helsinki, Finland.
  • Meriranta L; Helsinki University Hospital Cancer Center and University of Helsinki, Helsinki, Finland.
  • Karjalainen-Lindsberg ML; Helsinki University Hospital Cancer Center and University of Helsinki, Helsinki, Finland.
  • Nørgaard P; Herlev and Gentofte Hospital, Copenhagen University, Herlev, Denmark.
  • Pedersen M; Herlev and Gentofte Hospital, Copenhagen University, Herlev, Denmark.
  • Gang AO; Herlev and Gentofte Hospital, Copenhagen University, Herlev, Denmark.
  • Høgdall E; Herlev and Gentofte Hospital, Copenhagen University, Herlev, Denmark.
  • Heavican TB; Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA.
  • Lone W; Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA.
  • Iqbal J; Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA.
  • Qin Q; Duke Cancer Institute and Center for Genomic and Computational Biology, Duke University, Durham, NC, USA.
  • Li G; Duke Cancer Institute and Center for Genomic and Computational Biology, Duke University, Durham, NC, USA.
  • Kim SY; Duke Cancer Institute and Center for Genomic and Computational Biology, Duke University, Durham, NC, USA.
  • Healy J; Duke Cancer Institute and Center for Genomic and Computational Biology, Duke University, Durham, NC, USA.
  • Richards KL; Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC, USA.
  • Fedoriw Y; Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC, USA.
  • Bernal-Mizrachi L; Winship Cancer Institute, Emory University, Atlanta, GA, USA.
  • Koff JL; Winship Cancer Institute, Emory University, Atlanta, GA, USA.
  • Staton AD; Winship Cancer Institute, Emory University, Atlanta, GA, USA.
  • Flowers CR; Winship Cancer Institute, Emory University, Atlanta, GA, USA.
  • Paltiel O; Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
  • Goldschmidt N; Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
  • Calaminici M; Barts Cancer Institute of Queen Mary University of London, London, UK.
  • Clear A; Barts Cancer Institute of Queen Mary University of London, London, UK.
  • Gribben J; Barts Cancer Institute of Queen Mary University of London, London, UK.
  • Nguyen E; Pathology, Indiana University, Indianapolis, IN, USA.
  • Czader MB; Pathology, Indiana University, Indianapolis, IN, USA.
  • Ondrejka SL; Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH, USA.
  • Collie A; Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH, USA.
  • Hsi ED; Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH, USA.
  • Tse E; Queen Mary Hospital, University of Hong Kong, Hong Kong.
  • Au-Yeung RKH; Queen Mary Hospital, University of Hong Kong, Hong Kong.
  • Kwong YL; Queen Mary Hospital, University of Hong Kong, Hong Kong.
  • Srivastava G; Queen Mary Hospital, University of Hong Kong, Hong Kong.
  • Choi WWL; Queen Mary Hospital, University of Hong Kong, Hong Kong.
  • Evens AM; Tufts University Medical Center, Boston, MA, USA.
  • Pilichowska M; Tufts University Medical Center, Boston, MA, USA.
  • Sengar M; Tata Memorial Center, Mumbai, India.
  • Reddy N; Vanderbilt University Medical Center, Nashville, TN, USA.
  • Li S; MD Anderson Cancer Center, Houston, TX, USA.
  • Chadburn A; Columbia-Presbyterian Hospital, New York, NY, USA.
  • Gordon LI; Northwestern University Medical School, Chicago, IL, USA.
  • Jaffe ES; National Cancer Institute, Bethesda, MD, USA.
Cell ; 171(2): 481-494.e15, 2017 Oct 05.
Article en En | MEDLINE | ID: mdl-28985567
ABSTRACT
Diffuse large B cell lymphoma (DLBCL) is the most common form of blood cancer and is characterized by a striking degree of genetic and clinical heterogeneity. This heterogeneity poses a major barrier to understanding the genetic basis of the disease and its response to therapy. Here, we performed an integrative analysis of whole-exome sequencing and transcriptome sequencing in a cohort of 1,001 DLBCL patients to comprehensively define the landscape of 150 genetic drivers of the disease. We characterized the functional impact of these genes using an unbiased CRISPR screen of DLBCL cell lines to define oncogenes that promote cell growth. A prognostic model comprising these genetic alterations outperformed current established

methods:

cell of origin, the International Prognostic Index comprising clinical variables, and dual MYC and BCL2 expression. These results comprehensively define the genetic drivers and their functional roles in DLBCL to identify new therapeutic opportunities in the disease.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Linfoma de Células B Grandes Difuso / Perfilación de la Expresión Génica / Sistemas CRISPR-Cas Tipo de estudio: Prognostic_studies Límite: Female / Humans / Male Idioma: En Revista: Cell Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Linfoma de Células B Grandes Difuso / Perfilación de la Expresión Génica / Sistemas CRISPR-Cas Tipo de estudio: Prognostic_studies Límite: Female / Humans / Male Idioma: En Revista: Cell Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos