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Genetic and Functional Drivers of Diffuse Large B Cell Lymphoma

2017; Cell Press; Volume: 171; Issue: 2 Linguagem: Inglês

10.1016/j.cell.2017.09.027

1097-4172

Anupama Reddy, Jenny Zhang, Nicholas S. Davis, Andrea B. Moffitt, Cassandra Love, Alexander Waldrop, Sirpa Leppä, Annika Pasanen, Leo Meriranta, Marja-Liisa Karjalainen-Lindsberg, Peter Nørgaard, Mette Ølgod Pedersen, Anne Ortved 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 G. Gribben, Evelyn Nguyen, Magdalena Czader, Sarah L. Ondrejka, Angela M. B. Collie, Eric D. Hsi, Eric Tse, Rex 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 E. Rempel, Tiffany J. Tzeng, Lanie E. Happ, Tushar Dave, Deepthi Rajagopalan, Jyotishka Datta, David B. Dunson, Sandeep S. Davé,

Single-cell and spatial transcriptomics

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.