Neuroscience Consortium, University of Pavia, Monza Policlinico and Pavia Mondino, Pavia, Italy.
Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Inserm U 1127, CNRS UMR 7225, ICM.
Curr Opin Neurol. 2018 Dec;31(6):727-732. doi: 10.1097/WCO.0000000000000617.
Hotspot mutations of isocitrate dehydrogenase 1 (R132) or 2 (R172) genes affect 40% of diffuse gliomas, mostly grades II and III. The mutant enzyme produces high quantities of d-2-hydroxyglutarate (D2HG), which reshapes the epigenetic of the cell leading to gliomagenesis. For the clinician, the isocitrate dehydrogenase (IDH) mutation is a major biomarker with diagnostic, prognostic, and predictive consequences. With the development of specific inhibitors and vaccination, it appears also a potential actionable target.
IDH status is routinely determined on tumor sample by sequencing and immunohistochemistry detecting the most common mutant protein (IDH1R132H). Recently noninvasive diagnostic approaches have been developed based on the detection of the mutant DNA or the D2HG in body fluids, and the detection of D2HG by magnetic resonance spectroscopy of the brain.
These new techniques open avenues for non invasive diagnostic of glioma in patients not amenable to biopsy, in the preoperative setting and also duringpatients follow-up for evaluation of treatment response and prediction of recurrence.
异柠檬酸脱氢酶 1（R132）或 2（R172）基因突变热点影响 40%的弥漫性神经胶质瘤，主要为 2 级和 3 级。突变酶产生大量的 D-2-羟戊二酸（D2HG），重塑细胞的表观遗传学，导致神经胶质瘤发生。对于临床医生来说，异柠檬酸脱氢酶（IDH）突变是一个具有诊断、预后和预测意义的重要生物标志物。随着特异性抑制剂和疫苗的开发，它似乎也是一个潜在的可治疗靶点。
IDH 状态通常通过测序和免疫组织化学检测最常见的突变蛋白（IDH1R132H）来确定肿瘤样本中的状态。最近，已经开发出基于在体液中检测突变 DNA 或 D2HG 的非侵入性诊断方法，以及通过脑部磁共振波谱检测 D2HG 的方法。
这些新技术为无法进行活检的患者、术前以及患者随访期间的胶质瘤的非侵入性诊断开辟了道路，用于评估治疗反应和预测复发。
