| Literature DB >> 28985567 |
Anupama Reddy1, Jenny Zhang1, Nicholas S Davis2, Andrea B Moffitt2, Cassandra L Love2, Alexander Waldrop2, Sirpa Leppa3, Annika Pasanen3, Leo Meriranta3, Marja-Liisa Karjalainen-Lindsberg3, Peter Nørgaard4, Mette Pedersen4, Anne O Gang4, Estrid Høgdall4, Tayla B Heavican5, Waseem Lone5, Javeed Iqbal5, Qiu Qin2, Guojie Li2, So Young Kim2, Jane Healy2, Kristy L Richards6, Yuri Fedoriw6, Leon Bernal-Mizrachi7, Jean L Koff7, Ashley D Staton7, Christopher R Flowers7, Ora Paltiel8, Neta Goldschmidt8, Maria Calaminici9, Andrew Clear9, John Gribben9, Evelyn Nguyen10, Magdalena B Czader10, Sarah L Ondrejka11, Angela Collie11, Eric D Hsi11, Eric Tse12, Rex K H Au-Yeung12, Yok-Lam Kwong12, Gopesh Srivastava12, William W L Choi12, Andrew M Evens13, Monika Pilichowska13, Manju Sengar14, Nishitha Reddy15, Shaoying Li16, Amy Chadburn17, Leo I Gordon18, Elaine S Jaffe19, Shawn Levy20, Rachel Rempel2, Tiffany Tzeng2, Lanie E Happ2, Tushar Dave2, Deepthi Rajagopalan2, Jyotishka Datta2, David B Dunson21, Sandeep S Dave22.
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.Entities:
Keywords: DLBCL; TCGA; The Cancer Genome Atlas; diffuse large B cell lymphoma; exome sequencing; genetic mutations
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Year: 2017 PMID： 28985567 PMCID： PMC5659841 DOI： 10.1016/j.cell.2017.09.027
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582