Department of Medicine (Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale) - Molecular Diagnostic Unit, Azienda USL di Bologna, University of Bologna School of Medicine, Bologna, Italy.
Department of Pharmacy and Biotechnology (Dipartimento di Farmacia e Biotecnologie) - Molecular Diagnostic Unit, Azienda USL di Bologna, University of Bologna, Bologna, Italy.
Sci Rep. 2018 Mar 13;8(1):4459. doi: 10.1038/s41598-018-22222-y.
IDH mutational status is required for proper diagnosis according to the WHO criteria revised in 2016. The single nucleotide polymorphism (SNP) rs11554137 (IDH1) at codon 105 of IDH1 has been reported in patients with several tumor types, including those with glioma. The aim of this study is to investigate the prevalence of IDH1 in a cohort of brain tumors, and its association with clinicopathologic features and IDH1 and IDH2 missense mutations. Exon 4 of IDH1 and IDH2 was analyzed in a series of brain tumors classified according to current WHO criteria. DNA from control individuals was analyzed to infer the prevalence of IDH1 in the reference population. Analysis was performed using next generation sequencing. IDH1 was three times more frequent in patients with tumors (44/293 cases, 15.0%) vs. population controls (6/109, 5.5%) (p = 0.0102). IDH1 was more frequent in grade III tumors (26.1%) compared to grade II (10.9%, p = 0.038) and grade IV tumors (13.7%, p = 0.041). IDH1 was more frequent in grade II and III tumors without an IDH tumor missense mutation (43.8%) than in those with (11.5%, p = 0.005). The IDH1 SNP likely represents an important genetic marker, worthy of additional investigation to better understand the clinical and biological features of IDH-WT infiltrating gliomas.
根据 2016 年修订的世界卫生组织（WHO）标准，需要 IDH 突变状态来进行正确诊断。IDH1 第 105 位密码子的单核苷酸多态性（SNP）rs11554137（IDH1）已在多种肿瘤类型的患者中报道，包括胶质瘤患者。本研究旨在调查 IDH1 在脑肿瘤队列中的流行率，及其与临床病理特征以及 IDH1 和 IDH2 错义突变的相关性。根据当前的 WHO 标准对 IDH1 和 IDH2 的外显子 4 进行了分析。对来自对照个体的 DNA 进行了分析，以推断 IDH1 在参考人群中的流行率。分析使用了下一代测序技术。与人群对照（6/109，5.5%）相比，肿瘤患者中 IDH1 的频率高 3 倍（44/293 例，15.0%）（p=0.0102）。与 II 级肿瘤（10.9%，p=0.038）和 IV 级肿瘤（13.7%，p=0.041）相比，III 级肿瘤中 IDH1 的频率更高。与无 IDH 肿瘤错义突变的 II 级和 III 级肿瘤相比（43.8%），IDH1 的频率更高，而与具有 IDH 肿瘤错义突变的肿瘤相比（11.5%），IDH1 的频率更高（p=0.005）。IDH1 SNP 可能代表一个重要的遗传标志物，值得进一步研究以更好地了解 IDH-WT 浸润性神经胶质瘤的临床和生物学特征。
