Elena Trisolini1,2, Dounia El Wardighi3, Marine Giry3, Priscilla Bernardi1, Renzo Luciano Boldorini1, Karima Mokhtari4,5, Marc Sanson6,7,8. 1. Department of Health Sciences, Università del Piemonte Orientale, 28100, Novara, Italy. 2. Pathology Unit, Maggiore Della Carità Hospital, 28100, Novara, Italy. 3. Sorbonne Université, Inserm, CNRS, UMR S 1127, Institut du Cerveau Et de La Moelle épinière, ICM, AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Service de Neurologie 2-Mazarin, 75013, Paris, France. 4. AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Laboratoire de Neuropathologie R Escourolle, AP-HP, Groupe Hospitalier Pitié Salpêtrière, 75013, Paris, France. 5. Onconeurotek Tumor Bank, Institut du Cerveau et de la Moelle épinère -ICM, 75013, Paris, France. 6. Sorbonne Université, Inserm, CNRS, UMR S 1127, Institut du Cerveau Et de La Moelle épinière, ICM, AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Service de Neurologie 2-Mazarin, 75013, Paris, France. marc.sanson@aphp.fr. 7. Onconeurotek Tumor Bank, Institut du Cerveau et de la Moelle épinère -ICM, 75013, Paris, France. marc.sanson@aphp.fr. 8. Department of Neurology 2, GH Pitié-Salpêtrière, Paris, France. marc.sanson@aphp.fr.
Abstract
PURPOSE: Circumscribed gliomas -pilocytic astrocytomas (PA), gangliogliomas (GG), ependymomas (EP)- are mostly low-grade tumours but may progress to anaplasia and sometimes surgery can be challenging due to deep anatomical localization. Because of the high frequency of MAPK-pathway alterations and availability of targeted therapies for FGFR1 and BRAF-mutated tumors, we investigated these mutational hotspots in a cohort of adult circumscribed gliomas. METHODS: Adult patients (>15 years) with diagnosis of PA, GG, EP and DNET were retrospectively identified from two institutions databases. Genomic DNA was extracted from formalin-fixed paraffin-embedded or frozen samples and exons including codons 546 and 656 of FGFR1 and V600 of BRAF were sequenced. RESULTS: FGFR1 mutations were identified in 15/108 PA and were particularly frequent in optic pathway (6/9 vs. 9/108; p = 10-4). FGFR1 was mutated in 3/75 grade II versus 2/7 grade III GG (p = 0.05), 1/7 DNET, 1/100 EP grade II. We found 3/108 PA with BRAF pVal600Glu and 6/108 with p.Thr599_Val600insThr. The p.Val600Glu was found in 14/75 grade II GG. No EP were BRAF mutated. CONCLUSIONS: We report actionable targets, including frequent FGFR1 mutation in optic-pathway PA that makes them excellent candidates to anti-FGFR therapies, and BRAF non-canonical mutations in PA.
PURPOSE: Circumscribed gliomas -pilocytic astrocytomas (PA), gangliogliomas (GG), ependymomas (EP)- are mostly low-grade tumours but may progress to anaplasia and sometimes surgery can be challenging due to deep anatomical localization. Because of the high frequency of MAPK-pathway alterations and availability of targeted therapies for FGFR1 and BRAF-mutated tumors, we investigated these mutational hotspots in a cohort of adult circumscribed gliomas. METHODS: Adult patients (>15 years) with diagnosis of PA, GG, EP and DNET were retrospectively identified from two institutions databases. Genomic DNA was extracted from formalin-fixed paraffin-embedded or frozen samples and exons including codons 546 and 656 of FGFR1 and V600 of BRAF were sequenced. RESULTS:FGFR1 mutations were identified in 15/108 PA and were particularly frequent in optic pathway (6/9 vs. 9/108; p = 10-4). FGFR1 was mutated in 3/75 grade II versus 2/7 grade III GG (p = 0.05), 1/7 DNET, 1/100 EP grade II. We found 3/108 PA with BRAF pVal600Glu and 6/108 with p.Thr599_Val600insThr. The p.Val600Glu was found in 14/75 grade II GG. No EP were BRAF mutated. CONCLUSIONS: We report actionable targets, including frequent FGFR1 mutation in optic-pathway PA that makes them excellent candidates to anti-FGFR therapies, and BRAF non-canonical mutations in PA.
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