Genetic and Functional Drivers of Diffuse Large B Cell Lymphoma. Academic Article uri icon

Overview

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.

authors

publication date

  • October 5, 2017

Research

keywords

  • CRISPR-Cas Systems
  • Gene Expression Profiling
  • Lymphoma, Large B-Cell, Diffuse

Identity

PubMed Central ID

  • PMC5659841

Scopus Document Identifier

  • 85030529459

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2017.09.027

PubMed ID

  • 28985567

Additional Document Info

volume

  • 171

issue

  • 2