title: Droplet digital PCR is a powerful technique to demonstrate frequent FGFR1 duplication in dysembryoplastic neuroepithelial tumors.
abstract: 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. FGFR1G539R point mutation was only recorded in one DNT that also showed FGFR1-ITD. Interestingly, these FGFR1 alterations were mutually exclusive from BRAFV600E 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.
authors: Assistance Publique Hôpitaux de Marseille (AP-HM), Hôpital Nord, Service de Transfert d'Oncologie Biologique, Laboratoire de Biologie Médicale Marseille, France.
authors: Frédéric
authors: F
authors: Fina
authors: APHM, Hôpital de la Timone, Service d'Anatomie Pathologique et de Neuropathologie, Marseille, France.
authors: Doriane
authors: D
authors: Barets
authors: Aix-Marseille Université, Inserm, CRO2 UMR_S 911, Marseille, France.
authors: Carole
authors: C
authors: Colin
authors: APHM, Hôpital de la Timone, Service d'Anatomie Pathologique et de Neuropathologie, Marseille, France.|Aix-Marseille Université, Inserm, CRO2 UMR_S 911, Marseille, France.
authors: Corinne
authors: C
authors: Bouvier
authors: APHM, Hôpital de la Timone, Service de Radiothérapie, Marseille, France.
authors: Laëtitia
authors: L
authors: Padovani
authors: Assistance Publique Hôpitaux de Marseille (AP-HM), Hôpital Nord, Service de Transfert d'Oncologie Biologique, Laboratoire de Biologie Médicale Marseille, France.
authors: Isabelle
authors: I
authors: Nanni-Metellus
authors: Assistance Publique Hôpitaux de Marseille (AP-HM), Hôpital Nord, Service de Transfert d'Oncologie Biologique, Laboratoire de Biologie Médicale Marseille, France.
authors: L'Houcine
authors: L
authors: Ouafik
authors: APHM, Hôpital de la Timone, Service de Neurochirurgie Pédiatrique, Marseille, France.
authors: Didier
authors: D
authors: Scavarda
authors: Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors: Andrey
authors: A
authors: Korshunov
authors: Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors: David T W
authors: DT
authors: Jones
authors: APHM, Hôpital de la Timone, Service d'Anatomie Pathologique et de Neuropathologie, Marseille, France.|Aix-Marseille Université, Inserm, CRO2 UMR_S 911, Marseille, France.
authors: Dominique
authors: D
authors: Figarella-Branger
mesh_terms: D000293:Adolescent; D001254:Astrocytoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis / Q000379:methods*; D005260:Female; D018303:Ganglioglioma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020440:Gene Duplication; D005787:Gene Frequency; D005910:Glioma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D018302:Neoplasms, Neuroepithelial / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009837:Oligodendroglioma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016612:Paraffin Embedding; D017354:Point Mutation; D016133:Polymerase Chain Reaction / Q000379:methods*; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics* / Q000378:metabolism; D013724:Teratoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1
keywords: FGFR1; MAP kinase pathway; droplet digital PCR (DDPCR™); dysembryoplastic neuroepithelial tumor (DNT); low grade neuroepithelial tumor (LGNT)