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
Affiliations
Maria Guarnaccia
Institute for Biomedical Research and Innovation, National Research Council, Via P. Gaifami 18, 95126 Catania, Italy
Laura Guarnaccia
Laboratory of Experimental Neurosurgery and Cell Therapy, Neurosurgery Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy
Valentina La Cognata
Institute for Biomedical Research and Innovation, National Research Council, Via P. Gaifami 18, 95126 Catania, Italy
Stefania Elena Navone
Laboratory of Experimental Neurosurgery and Cell Therapy, Neurosurgery Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy
Rolando Campanella
Laboratory of Experimental Neurosurgery and Cell Therapy, Neurosurgery Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy
Antonella Ampollini
Laboratory of Experimental Neurosurgery and Cell Therapy, Neurosurgery Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy
Marco Locatelli
Laboratory of Experimental Neurosurgery and Cell Therapy, Neurosurgery Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy
Monica Miozzo
Department of Health Sciences, University of Milan, 20122 Milan, Italy
Giovanni Marfia
Laboratory of Experimental Neurosurgery and Cell Therapy, Neurosurgery Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy
Sebastiano Cavallaro
Institute for Biomedical Research and Innovation, National Research Council, Via P. Gaifami 18, 95126 Catania, Italy
Gliomas account for the majority of primary brain tumors. Glioblastoma is the most common 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 chromosomes 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.