Genetic and Functional Drivers of Diffuse Large B Cell Lymphoma.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Reddy, A; Zhang, J; Davis, NS; Moffitt, AB; Love, CL; Waldrop, A; Leppa, S; Pasanen, A; Meriranta, L; Karjalainen-Lindsberg, M-L; Nørgaard, P; Pedersen, M; Gang, AO; Høgdall, E; Heavican, TB; Lone, W; Iqbal, J; Qin, Q; Li, G; Kim, SY; Healy, J; Richards, KL; Fedoriw, Y; Bernal-Mizrachi, L; Koff, JL; Staton, AD; Flowers, CR; Paltiel, O; Goldschmidt, N; Calaminici, M; Clear, A; Gribben, J; Nguyen, E; Czader, MB; Ondrejka, SL; Collie, A; Hsi, ED; Tse, E; Au-Yeung, RKH; Kwong, Y-L; Srivastava, G; Choi, WWL; Evens, AM; Pilichowska, M; Sengar, M; Reddy, N; Li, S; Chadburn, A; Gordon, LI; Jaffe, ES; Levy, S; Rempel, R; Tzeng, T; Happ, LE; Dave, T; Rajagopalan, D; Datta, J; Dunson, DB; Dave, SS

Published Date

  • October 5, 2017

Published In

Volume / Issue

  • 171 / 2

Start / End Page

  • 481 - 494.e15

PubMed ID

  • 28985567

Pubmed Central ID

  • PMC5659841

Electronic International Standard Serial Number (EISSN)

  • 1097-4172

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2017.09.027

Language

  • eng

Conference Location

  • United States