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Genetic and Functional Drivers of Diffuse Large B Cell Lymphoma

Authors :
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
Levy, Shawn
Rempel, Rachel
Tzeng, Tiffany
Happ, Lanie E.
Dave, Tushar
Rajagopalan, Deepthi
Datta, Jyotishka
Dunson, David B.
Dave, Sandeep S.
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
Levy, Shawn
Rempel, Rachel
Tzeng, Tiffany
Happ, Lanie E.
Dave, Tushar
Rajagopalan, Deepthi
Datta, Jyotishka
Dunson, David B.
Dave, Sandeep S.
Source :
Reddy , A , Zhang , J , Davis , N S , Moffitt , A B , Love , C L , Waldrop , A , Leppa , S , Pasanen , A , Meriranta , L , Karjalainen-Lindsberg , M-L , Nørgaard , P , Pedersen , M , Gang , A O , Høgdall , E , Heavican , T B , Lone , W , Iqbal , J , Qin , Q , Li , G , Kim , S Y , Healy , J , Richards , K L , Fedoriw , Y , Bernal-Mizrachi , L , Koff , J L , Staton , A D , Flowers , C R , Paltiel , O , Goldschmidt , N , Calaminici , M , Clear , A , Gribben , J , Nguyen , E , Czader , M B , Ondrejka , S L , Collie , A , Hsi , E D , Tse , E , Au-Yeung , R K H , Kwong , Y-L , Srivastava , G , Choi , W W L , Evens , A M , Pilichowska , M , Sengar , M , Reddy , N , Li , S , Chadburn , A , Gordon , L I , Jaffe , E S , Levy , S , Rempel , R , Tzeng , T , Happ , L E , Dave , T , Rajagopalan , D , Datta , J , Dunson , D B & Dave , S S 2017 , ' Genetic and Functional Drivers of Diffuse Large B Cell Lymphoma ' , Cell , vol. 171 , no. 2 , pp. 481-494.e15 .
Publication Year :
2017

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.

Details

Database :
OAIster
Journal :
Reddy , A , Zhang , J , Davis , N S , Moffitt , A B , Love , C L , Waldrop , A , Leppa , S , Pasanen , A , Meriranta , L , Karjalainen-Lindsberg , M-L , Nørgaard , P , Pedersen , M , Gang , A O , Høgdall , E , Heavican , T B , Lone , W , Iqbal , J , Qin , Q , Li , G , Kim , S Y , Healy , J , Richards , K L , Fedoriw , Y , Bernal-Mizrachi , L , Koff , J L , Staton , A D , Flowers , C R , Paltiel , O , Goldschmidt , N , Calaminici , M , Clear , A , Gribben , J , Nguyen , E , Czader , M B , Ondrejka , S L , Collie , A , Hsi , E D , Tse , E , Au-Yeung , R K H , Kwong , Y-L , Srivastava , G , Choi , W W L , Evens , A M , Pilichowska , M , Sengar , M , Reddy , N , Li , S , Chadburn , A , Gordon , L I , Jaffe , E S , Levy , S , Rempel , R , Tzeng , T , Happ , L E , Dave , T , Rajagopalan , D , Datta , J , Dunson , D B & Dave , S S 2017 , ' Genetic and Functional Drivers of Diffuse Large B Cell Lymphoma ' , Cell , vol. 171 , no. 2 , pp. 481-494.e15 .
Notes :
English
Publication Type :
Electronic Resource
Accession number :
edsoai.on1322712194
Document Type :
Electronic Resource