Determination of ETV6-RUNX1 genomic breakpoint by next-generation sequencing

Cancer Med. 2016 Feb;5(2):337-51. doi: 10.1002/cam4.579. Epub 2015 Dec 29.

Abstract

The t(12;21)(p13;q22) ETV6-RUNX1 gene fusion is one of the most common chromosomal translocation in childhood acute lymphoblastic leukemia (ALL). It is associated with favorable prognosis. The identification of the genomic sequence of the breakpoint flanking regions of the ETV6-RUNX1 translocation should be the best strategy to monitor minimal residual disease (MRD) in patients with ETV6-RUNX1-positive ALL. In this study, the ETV6-RUNX1 translocation was sequenced by next-generation sequencing (NGS) in 26 patients with ETV6-RUNX1-positive ALL and re-sequenced by using the Sanger method. Interestingly, the three-way translocation, including ETV6-RUNX1, was detected in five patients. Four of them relapsed during or after therapy, while 21 patients without the three-way translocation were still in remission (P < 0.0001). The three-way translocation pattern was identical between the diagnosis and relapse samples in three patients, excluding one patient (SCMC-001245). The relapse samples retained the translocation of ETV6-RUNX1 relative to the three-way translocation t(8;12;21) at diagnosis, suggesting that the three-way translocation might be an important risk factor for relapse in patients with ETV6-RUNX1-positive ALL and should be further studied.

Keywords: Acute lymphoblastic leukemia; ETV6-RUNX1; breakpoint; childhood; next-generation sequencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Marrow / pathology
  • Child
  • Child, Preschool
  • Chromosome Breakpoints*
  • Chromosomes, Human, Pair 12
  • Chromosomes, Human, Pair 21
  • Clonal Evolution
  • Core Binding Factor Alpha 2 Subunit / genetics*
  • Female
  • Gene Order
  • Genetic Loci
  • High-Throughput Nucleotide Sequencing*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Infant
  • Male
  • Oncogene Proteins, Fusion / genetics*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / diagnosis
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Recurrence
  • Translocation, Genetic

Substances

  • Core Binding Factor Alpha 2 Subunit
  • Oncogene Proteins, Fusion
  • TEL-AML1 fusion protein