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Region Hovedstaden - en del af Københavns Universitetshospital
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Genetic and Functional Drivers of Diffuse Large B Cell Lymphoma

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

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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
Vis graf over relationer

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.

OriginalsprogEngelsk
TidsskriftCell
Vol/bind171
Udgave nummer2
Sider (fra-til)481-494.e15
ISSN0092-8674
DOI
StatusUdgivet - 5 okt. 2017

ID: 52353183