Cell
Volume 171, Issue 2, 5 October 2017, Pages 481-494.e15
Journal home page for Cell

Resource
Genetic and Functional Drivers of Diffuse Large B Cell Lymphoma

https://doi.org/10.1016/j.cell.2017.09.027Get rights and content
Under an Elsevier user license
open archive

Highlights

  • Exome sequencing in 1,001 DLBCL patients comprehensively identifies 150 driver genes

  • Unbiased CRISPR screen in DLBCL cell lines identifies essential oncogenes

  • Integrative analysis connects genomics, CRISPR hits, and clinical outcome

  • A genomic risk model of survival outperforms existing risk-assessment methods

Summary

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.

Keywords

exome sequencing
genetic mutations
diffuse large B cell lymphoma
DLBCL
TCGA
The Cancer Genome Atlas

Cited by (0)

22

These authors contributed equally

23

Lead Contact