CNR ExploRA

Articolo in rivista, 2022, ENG, 10.3390/ life12070956

A Targeted Next-Generation Sequencing Panel to Genotype Gliomas

Maria Guarnaccia; Laura Guarnaccia; Valentina La Cognata; Stefania Elena Navone; Rolando Campanella; Antonella Ampollini; Marco Locatelli; Monica Miozzo; Giovanni Marfia; Sebastiano Cavallaro;

Institute for Biomedical Research and Innovation, National Research Council, Via P. Gaifami 18, 95126 Catania, Italy; maria.guarnaccia@cnr.it (M.G.); valentina.lacognata@cnr.it (V.L.C.) 2 Laboratory of Experimental Neurosurgery and Cell Therapy, Neurosurgery Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy; laura.guarnaccia@policlinico.mi.it (L.G.); stefania.navone@policlinico.mi.it (S.E.N.); campanella.rolando@gmail.com (R.C.); antonella.ampollini@policlinico.mi.it (A.A.); marco.locatelli@policlinico.mi.it (M.L.); giovanni.marfia@policlinico.mi.it (G.M.) 3 Department of Clinical Sciences and Community Health, University of Milan, Via Festa del Perdono 7, 20122 Milan, Italy 4 "Aldo Ravelli" Research Center, Via Antonio di Rudinì 8, 20142 Milan, Italy 5 Department of Medical-Surgical Physiopathology and Transplantation, University of Milan, Via Francesco Sforza 35, 20122 Milan, Italy 6 Department of Health Sciences, University of Milan, 20122 Milan, Italy; monica.miozzo@unimi.it 7 Unit of Medical Genetics, ASST Santi Paolo e Carlo, 20142 Milan, Italy 8 Clinical Pathology Unit, Aerospace Medicine Institute "A. Mosso", Italian Air Force, Viale dell'Aviazione 1, 20138 Milan, Italy

Gliomas account for the majority of primary brain tumors. Glioblastoma is the most com- mon and malignant type. Based on their extreme molecular heterogeneity, molecular markers can be used to classify gliomas and stratify patients into diagnostic, prognostic, and therapeutic clusters. In this work, we developed and validated a targeted next-generation sequencing (NGS) approach to analyze variants or chromosomal aberrations correlated with tumorigenesis and response to treatment in gliomas. Our targeted NGS analysis covered 13 glioma-related genes (ACVR1, ATRX, BRAF, CDKN2A, EGFR, H3F3A, HIST1H3B, HIST1H3C, IDH1, IDH2, P53, PDGFRA, PTEN), a 125 bp region of the TERT promoter, and 54 single nucleotide polymorphisms (SNPs) along chromo- somes 1 and 19 for reliable assessment of their copy number alterations (CNAs). Our targeted NGS approach provided a portrait of gliomas' molecular heterogeneity with high accuracy, specificity, and sensitivity in a single workflow, enabling the detection of variants associated with unfavorable outcomes, disease progression, and drug resistance. These preliminary results support its use in routine diagnostic neuropathology.

Life (Basel)