Next generation sequencing identifies novel potential actionable mutations for grade I meningioma treatment
Francesco Pepe1*, Pasquale Pisapia1*, Maria Laura Del Basso de Caro2, Floriana Conticelli1, Umberto Malapelle1, Giancarlo Troncone1 and Juan Carlos Martinez3
1Department of Public Health, 2Department of Advanced Biomedical Sciences, University of Naples "Federico II", Naples, Italy and 3Department of Pathology, Gregorio Maraņon University Hospital, Madrid, Spain
*These authors contributed equally
Offprint requests to: Giancarlo Troncone, Department of Public Health, University of Naples Federico II, Via Sergio Pansini 5, 80131 Naples, Italy. e-mail: giancarlo.troncone@unina.it
Summary. Meningiomas are common brain tumors that arise from the meningeal membranes that envelope the brain and spinal cord. The World Health Organization classifies these tumors into three histopathological grades. Because of tumor recurrence, treating meningiomas may be challenging even in well-differentiated grade I (GI) neoplasms. Indeed, around 5% of completely resected GI meningiomas relapse within 5 years. Therefore, identifying driver mutations in GI meningiomas through next generation sequencing (NGS) assays is paramount. The aim of this study was to validate the use of the 50-gene AmpliSeq Hotspot Cancer Panel v2 to identify the mutational status of 23 GI meningioma, namely, 12 non recurrent and 11 recurrent. In 18 out of the 23 GI meningiomas analyzed, we identified at least one gene mutation (78.2%). The most frequently mutated genes were c-kit (39.1%), ATM (26.1%), TP53 (26.1%), EGFR (26.1%), STK11 (21.7%), NRAS (17.4%), SMAD4 (13%), FGFR3 (13%), and PTPN11 (13%); less frequent mutations were SMARCB1 (8.7%), FLT3 (8.7%), KRAS (8.7%), FBWX7 (8.7%), ABL1 (8.7%), ERBB2 (8.7%), IDH1 (8.7%), BRAF (8.7%), MET (8.7%), HRAS (4.3%), RB1 (4.3%), CTNNB1 (4.3%), PIK3CA (4.3%), VHL (4.3%), KDR (4.3%), APC (4.3%), NOTCH1 (4.3%), JAK3 (4.3%), and SRC (4.3%). To our knowledge, mutations in all of these genes, except for TP53, STK11, SMARCB1, PIK3CA, VHL, and BRAF, have never been described before in meningiomas. Hence, these findings demonstrate the viability of NGS to detect new genetic alterations in GI meningiomas. Equally important, this technology enabled us to detect possible novel actionable mutations not previously associated with GI and for which selective inhibitors already exist. Histol Histopathol 35, 741-749 (2020)
Key words: NGS, Biomarkers, Meningiomas
DOI: 10.14670/HH-18-195