Droplet digital PCR is a powerful technique to demonstrate frequent <i>FGFR1</i> duplication in dysembryoplastic neuroepithelial tumors


  • Fina Frédéric
  • Barets Doriane
  • Colin Carole
  • Bouvier Corinne
  • Padovani Laëtitia
  • Nanni-Metellus Isabelle
  • Ouafik l'Houcine
  • Scavarda Didier
  • Korshunov Andrey
  • Jones T.W David
  • Figarella-Branger Dominique


  • Dysembryoplastic neuroepithelial tumor DNT
  • Low grade neuroepithelial tumor LGNT
  • FGFR1
  • Droplet digital PCR DDPCR™
  • MAP kinase pathway

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Dysembryoplastic neuroepithelial tumors (DNT) share V600E mutation in the BRAF gene with other low grade neuroepithelial tumors (LGNTs). FGFR1 internal tandem duplication of the tyrosine-kinase domain (FGFR1-ITD), another genetic alteration that also leads to MAP kinase pathway alteration, has been previously reported in LGNTs by whole-genome sequencing. In the present study we searched for FGFR1-ITD by droplet digital PCR (DDPCR™) and for FGFR1 point mutations by HRM-sequencing in a series of formalin-fixed paraffin-embedded (FFPE) LGNTs including 12 DNT, 2 oligodendrogliomas lacking IDH mutation and 1p/19q co-deletion (pediatric-type oligodendrogliomas; PTOs), 3 pediatric diffuse astrocytomas (PDAs), 14 gangliogliomas (GGs) and 5 pilocytic astrocytomas (PAs). We showed by DDPCR™ that 5/12 DNT, but none of the other LGNTs, demonstrated FGFR1-ITD. In addition, these cases also accumulated phosphorylated-FGFR1 protein as shown by immunohistochemistry. FGFR1 G539R point mutation was only recorded in one DNT that also showed FGFR1-ITD. Interestingly, these FGFR1 alterations were mutually exclusive from BRAF V600E mutation that was recorded in 13 LGNTs (3 DNTs, 1 PTO, 2 PDAs, 5 GGs and 2 PAs). Therefore, FGFR1 alteration mainly represented by FGFR1-ITD is a frequent event in DNT. DDPCR™ is an easy and alternative method than whole-genome sequencing to detect FGFR1-ITD in FFPE brain tumors, in routine practice.

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