A Custom DNA-Based NGS Panel for the Molecular Characterization of Patients With Diffuse Gliomas: Diagnostic and Therapeutic Applications

• DOI: 10.3389/fonc.2022.861078
• Publication Date: 2022-03-17T13:02:48Z
• Authors: Elena Tirrò; Michele Massimino; Giuseppe Broggi; Chiara Romano; Simone Minasi; Francesca Gianno; Manila Antonelli; Gianmarco Motta; Francesco Certo; Roberto Altieri; Livia Manzella; Rosario Caltabiano; Giuseppe Maria Vi...; Francesca Romana ...; Gaetano Magro; Felice Giangaspero; Paolo Vigneri
• Keywords: ATRX; Isocitrate dehydrogenase

The management of patients with Central Nervous System (CNS) malignancies relies on the appropriate classification these tumors. Recently, World Health Organization (WHO) has published new criteria underlining importance an accurate molecular characterization CNS malignancies, in order to integrate information generated by histology. Next generation sequencing (NGS) allows single step multiple genes, generating a comprehensive and specific mutational profile tumor tissue. We developed custom NGS-based multi-gene panel (Glio-DNA panel) for identification correct glioma oncotype detection its essential aberrations. Specifically, Glio-DNA targets genetic chromosomal alterations involving ATRX chromatin remodeler (ATRX), cyclin dependent kinase inhibitor 2A (CDKN2A), isocitrate dehydrogenase (NADP+) 1 (IDH1) telomerase reverse transcriptase (TERT) promoter while also recognizing co-deletion 1p/19q, loss chromosome 10 gain 7. Furthermore, evaluates methylation level O-6-methylguanine-DNA methyltransferase (MGMT) gene that predicts temozolomide efficacy. As knowledge landscape each is mandatory define personalized therapeutic strategy, identifies "druggable" or "actionable" genes. To test specificity our panel, we used two reference mutated DNAs verifying NGS allele frequency measurement was highly sensitive. Subsequently, performed comparative analysis between conventional techniques - such as immunohistochemistry fluorescence situ hybridization 60 diffuse samples had been previously characterized. comparison testing showed high concordance, suggesting may replace time-consuming tests. Finally, different actionable genes matches potential targeted therapies available through clinical trials. In conclusion, demonstrates efficacy simultaneously detecting useful diagnosis, prognosis treatment adult glioma.