Genetic and Functional Drivers of Diffuse Large B Cell Lymphoma

Publication date: 5 October 2017
Source:Cell, Volume 171, Issue 2
Author(s): 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
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.

Graphical abstract

Teaser

An integrative analysis in 1,001 newly diagnosed DLBCL patients identifies 150 genetic drivers with functional characterization using an unbiased CRISPR screen in DLBCL cell lines and connects with clinical outcome.


from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2ykRRz4
via IFTTT