Multiplex ligation-dependent probe amplification analysis is useful for detecting a copy number gain of the FGFR1 tyrosine kinase domain in dysembryoplastic neuroepithelial tumors

J Neurooncol. 2019 May;143(1):27-33. doi: 10.1007/s11060-019-03138-7. Epub 2019 Mar 1.

Abstract

Purpose: Dysembryoplastic neuroepithelial tumors (DNTs) are slow-growing glioneuronal tumors, and their genetic backgrounds are getting unveiled. Recently, fibroblast growth factor receptor 1 internal tandem duplication (FGFR1-ITD) of the tyrosine kinase domain (TKD) has been demonstrated by whole-genome sequencing.

Methods and results: Here, we analyzed 22 DNTs using multiplex ligation-dependent probe amplification (MLPA) with formalin-fixed paraffin-embedded specimens and found a copy number gain in TKD of FGFR1 (13 cases, 59%), which suggested the presence of FGFR1-ITD. Another 5 DNTs harbored FGFR1 hot spot mutations including a double mutant case, and FGFR1 alterations were detected in 18 DNTs (82%). The BRAF V600E mutation, another important mutation in DNTs, was not observed.

Conclusions: With recent findings of less frequent or absent FGFR1-ITD in pilocytic astrocytomas or rosette-forming glioneuronal tumors, the analysis of FGFR1 aberrations, especially FGFR1-ITD, was suggested to be helpful to discriminate DNTs from their histological mimics.

Keywords: DNT; FFPE; FGFR1 alteration; FGFR1-ITD; MLPA.

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers, Tumor / genetics
  • Child
  • Child, Preschool
  • Class I Phosphatidylinositol 3-Kinases / genetics
  • DNA Copy Number Variations*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Multiplex Polymerase Chain Reaction* / methods
  • Mutation*
  • Neoplasms, Neuroepithelial / diagnosis
  • Neoplasms, Neuroepithelial / genetics*
  • Neoplasms, Neuroepithelial / pathology
  • Protein Domains
  • Proto-Oncogene Proteins B-raf / genetics
  • Receptor, Fibroblast Growth Factor, Type 1 / genetics*
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human
  • FGFR1 protein, human
  • Receptor, Fibroblast Growth Factor, Type 1
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf