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The Capital Region of Denmark - a part of Copenhagen University Hospital
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Genetic and Functional Drivers of Diffuse Large B Cell Lymphoma

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  • Anupama Reddy
  • Jenny Zhang
  • Nicholas S Davis
  • Andrea B Moffitt
  • Cassandra L Love
  • Alexander Waldrop
  • Sirpa Leppa
  • Annika Pasanen
  • Leo Meriranta
  • Marja-Liisa Karjalainen-Lindsberg
  • Peter Nørgaard
  • Mette Pedersen
  • Anne O Gang
  • Estrid Høgdall
  • Tayla B Heavican
  • Waseem Lone
  • Javeed Iqbal
  • Qiu Qin
  • Guojie Li
  • So Young Kim
  • Jane Healy
  • Kristy L Richards
  • Yuri Fedoriw
  • Leon Bernal-Mizrachi
  • Jean L Koff
  • Ashley D Staton
  • Christopher R Flowers
  • Ora Paltiel
  • Neta Goldschmidt
  • Maria Calaminici
  • Andrew Clear
  • John Gribben
  • Evelyn Nguyen
  • Magdalena B Czader
  • Sarah L Ondrejka
  • Angela Collie
  • Eric D Hsi
  • Eric Tse
  • Rex K H Au-Yeung
  • Yok-Lam Kwong
  • Gopesh Srivastava
  • William W L Choi
  • Andrew M Evens
  • Monika Pilichowska
  • Manju Sengar
  • Nishitha Reddy
  • Shaoying Li
  • Amy Chadburn
  • Leo I Gordon
  • Elaine S Jaffe
  • Shawn Levy
  • Rachel Rempel
  • Tiffany Tzeng
  • Lanie E Happ
  • Tushar Dave
  • Deepthi Rajagopalan
  • Jyotishka Datta
  • David B Dunson
  • Sandeep S Dave
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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.

Original languageEnglish
JournalCell
Volume171
Issue number2
Pages (from-to)481-494.e15
ISSN0092-8674
DOIs
Publication statusPublished - 5 Oct 2017

    Research areas

  • Antineoplastic Agents, CRISPR-Cas Systems, Cell Line, Tumor, Cells, Cultured, Exome, Female, Gene Expression Profiling, Humans, Lymphoma, Large B-Cell, Diffuse, Male, Rituximab, Journal Article

ID: 52353183