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

Frédéric Fina (1) , Doriane Barets (2) , Carole Colin (3) , Corinne Bouvier (2, 3) , Laëtitia Padovani (4, 5) , Isabelle Nanni-Metellus (1) , L'Houcine Ouafik (1) , Didier Scavarda (6) , Andrey Korshunov (7) , T.W David T W Jones (7) , Dominique Figarella-Branger (3, 2)

1 Laboratoire de Transfert en Oncologie Biologique
2 ACPNP - Service d'Anatomo-Cyto-Pathologie et de NeuroPathologie [Hôpital de la Timone - APHM]
3 CRO2 - Centre de Recherches en Oncologie biologique et Oncopharmacologie
4 TIMONE - Hôpital de la Timone [CHU - APHM]
5 Service de radiothérapie - [Hôpital de la Timone - Hôpital Nord - APHM]
6 Service de pédiatrie spécialisée et médecine infantile (neurologie, pneumologie, maladies héréditaires du métabolisme) [Hôpital de la Timone - APHM]
7 Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

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.

Mots clés: dysembryoplastic neuroepithelial tumor (DNT); low grade neuroepithelial tumor (LGNT); FGFR1; droplet digital PCR (DDPCR™); MAP kinase pathway

Domaines: Médecine humaine et pathologie

Frédéric Fina, Doriane Barets, Carole Colin, Corinne Bouvier, Laëtitia Padovani, et al.. Droplet digital PCR is a powerful technique to demonstrate frequent FGFR1 duplication in dysembryoplastic neuroepithelial tumors. Oncotarget, 2016, ⟨10.18632/oncotarget.12881⟩. ⟨hal-01478869⟩