Research Papers:

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

Frédéric Fina, Doriane Barets, Carole Colin, Corinne Bouvier, Laëtitia Padovani, Isabelle Nanni-Metellus, L’Houcine Ouafik, Didier Scavarda, Andrey Korshunov, David T.W. Jones and Dominique Figarella-Branger _

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Oncotarget. 2017; 8:2104-2113. https://doi.org/10.18632/oncotarget.12881

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Frédéric Fina1, Doriane Barets2, Carole Colin3, Corinne Bouvier2,3, Laëtitia Padovani4, Isabelle Nanni-Metellus1, L’Houcine Ouafik1, Didier Scavarda5, Andrey Korshunov6, David T.W. Jones6, Dominique Figarella-Branger2,3

1Assistance Publique Hôpitaux de Marseille (AP-HM), Hôpital Nord, Service de Transfert d'Oncologie Biologique, Laboratoire de Biologie Médicale Marseille, France

2APHM, Hôpital de la Timone, Service d’Anatomie Pathologique et de Neuropathologie, Marseille, France

3Aix-Marseille Université, Inserm, CRO2 UMR_S 911, Marseille, France

4APHM, Hôpital de la Timone, Service de Radiothérapie, Marseille, France

5APHM, Hôpital de la Timone, Service de Neurochirurgie Pédiatrique, Marseille, France

6Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

Correspondence to:

Dominique Figarella-Branger, email: [email protected]

Keywords: dysembryoplastic neuroepithelial tumor (DNT), low grade neuroepithelial tumor (LGNT), FGFR1, droplet digital PCR (DDPCR™), MAP kinase pathway

Received: June 15, 2016     Accepted: October 13, 2016     Published: October 25, 2016


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.

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