Identification of ETV6-RUNX1-like and DUX4-rearranged subtypes in paediatric B-cell precursor acute lymphoblastic leukaemia

Nat Commun. 2016 Jun 6:7:11790. doi: 10.1038/ncomms11790.

Abstract

Fusion genes are potent driver mutations in cancer. In this study, we delineate the fusion gene landscape in a consecutive series of 195 paediatric B-cell precursor acute lymphoblastic leukaemia (BCP ALL). Using RNA sequencing, we find in-frame fusion genes in 127 (65%) cases, including 27 novel fusions. We describe a subtype characterized by recurrent IGH-DUX4 or ERG-DUX4 fusions, representing 4% of cases, leading to overexpression of DUX4 and frequently co-occurring with intragenic ERG deletions. Furthermore, we identify a subtype characterized by an ETV6-RUNX1-like gene-expression profile and coexisting ETV6 and IKZF1 alterations. Thus, this study provides a detailed overview of fusion genes in paediatric BCP ALL and adds new pathogenetic insights, which may improve risk stratification and provide therapeutic options for this disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing / genetics
  • Child
  • Chromosome Breakage
  • Cluster Analysis
  • Cohort Studies
  • DNA Mutational Analysis
  • Gene Expression Regulation, Neoplastic
  • Gene Rearrangement / genetics*
  • Gene Regulatory Networks
  • Homeodomain Proteins / genetics*
  • Humans
  • Oncogene Proteins, Fusion / genetics*
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Principal Component Analysis

Substances

  • DUX4L1 protein, human
  • Homeodomain Proteins
  • Oncogene Proteins, Fusion