Guarnaccia Maria, Guarnaccia Laura, La Cognata Valentina, Navone Stefania Elena, Campanella Rolando, Ampollini Antonella, Locatelli Marco, Miozzo Monica, Marfia Giovanni, Cavallaro Sebastiano
Institute for Biomedical Research and Innovation, National Research Council, Via P. Gaifami 18, 95126 Catania, Italy.
Laboratory of Experimental Neurosurgery and Cell Therapy, Neurosurgery Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy.
Life (Basel). 2022 Jun 24;12(7):956. doi: 10.3390/life12070956.
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 (, , , , , , , , , , , , ), a 125 bp region of the 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.
神经胶质瘤占原发性脑肿瘤的大多数。胶质母细胞瘤是最常见且恶性程度最高的类型。基于其极端的分子异质性，分子标志物可用于对神经胶质瘤进行分类，并将患者分层到诊断、预后和治疗组中。在这项工作中，我们开发并验证了一种靶向新一代测序（NGS）方法，以分析与神经胶质瘤发生及治疗反应相关的变异或染色体畸变。我们的靶向NGS分析涵盖了13个神经胶质瘤相关基因（，，，，，，，，，，，，）、启动子的一个125 bp区域，以及1号和19号染色体上的54个单核苷酸多态性（SNP），以便可靠地评估其拷贝数改变（CNA）。我们的靶向NGS方法在单个工作流程中以高精度、特异性和敏感性描绘了神经胶质瘤的分子异质性，能够检测与不良预后、疾病进展和耐药性相关的变异。这些初步结果支持其在常规诊断神经病理学中的应用。
