PDF(Pubmed)
Abstract：
Molecular markers for classification of gliomas include isocitrate dehydrogenase (IDH) mutations and codeletion of chromosomal arms 1p and 19q (1p/19q). While mutations in IDH enzymes result in the well-characterized production of oncometabolite 2-hydroxyglutarate, dysregulation of other metabolites in IDH tumors is less characterized. Similarly, the effects of 1p/19q codeletion on cellular metabolism are also unclear.
This study aimed to quantify changes in tumor metabolites in human glioma tissue as a function of both IDH mutation and 1p/19q codeletion.
Deidentified human glioma tissue and associated clinical data were obtained from the Emory University Winship Cancer Institute tissue biobank from 14 patients (WHO grades II, III, and IV; seven female and seven male). Proton (1 H) high-resolution magic angle spinning (HR-MAS) nuclear magnetic resonance (NMR) spectroscopy data were acquired using a 600 MHz Bruker AVANCE III NMR spectrometer. Metabolite concentrations were calculated using LCModel. Differences in metabolite concentrations as a function of IDH mutation, 1p/19q codeletion, and survival status were determined using Mann-Whitney U tests. Concentrations of alanine, glutamine, and glutamate were significantly lower in glioma tissue with IDH mutations compared to tissue with IDH wildtype. Additionally, glutamate concentration was significantly lower in glioma tissue with 1p/19q codeletion compared to intact 1p/19q. Exploratory analysis revealed alanine concentration varied significantly as a function of survival status.
Given the emerging landscape of glioma treatments that target metabolic dysregulation, an improved understanding of altered metabolism in molecular sub-types of gliomas, including those with IDH mutation and 1p/19q codeletion, is an important consideration for treatment stratification and personalized medicine.
This study aimed to quantify changes in tumor metabolites in human glioma tissue as a function of both IDH mutation and 1p/19q codeletion.
Deidentified human glioma tissue and associated clinical data were obtained from the Emory University Winship Cancer Institute tissue biobank from 14 patients (WHO grades II, III, and IV; seven female and seven male). Proton (1 H) high-resolution magic angle spinning (HR-MAS) nuclear magnetic resonance (NMR) spectroscopy data were acquired using a 600 MHz Bruker AVANCE III NMR spectrometer. Metabolite concentrations were calculated using LCModel. Differences in metabolite concentrations as a function of IDH mutation, 1p/19q codeletion, and survival status were determined using Mann-Whitney U tests. Concentrations of alanine, glutamine, and glutamate were significantly lower in glioma tissue with IDH mutations compared to tissue with IDH wildtype. Additionally, glutamate concentration was significantly lower in glioma tissue with 1p/19q codeletion compared to intact 1p/19q. Exploratory analysis revealed alanine concentration varied significantly as a function of survival status.
Given the emerging landscape of glioma treatments that target metabolic dysregulation, an improved understanding of altered metabolism in molecular sub-types of gliomas, including those with IDH mutation and 1p/19q codeletion, is an important consideration for treatment stratification and personalized medicine.
摘要：
背景：神经胶质瘤分类的分子标记包括异柠檬酸脱氢酶（IDH）突变和染色体臂1p和19q（1p/19q）的共缺失。虽然IDH酶中的突变导致细胞代谢产物2-羟基戊二酸的充分表征的产生，IDH肿瘤中其他代谢物的失调特征较少。同样，1p/19q共缺失对细胞代谢的影响也不清楚.
目的：本研究旨在量化人神经胶质瘤组织中肿瘤代谢物的变化，作为IDH突变和1p/19q共缺失的函数。
结果：鉴定的人类神经胶质瘤组织和相关的临床数据是从埃默里大学Winship癌症研究所组织生物库获得的，来自14名患者（WHOII级，III,和IV；七个女性和七个男性）。使用600MHzBrukerAVANCEIIINMR光谱仪获得质子(1H)高分辨率幻角旋转(HR-MAS)核磁共振(NMR)光谱数据。使用LCModel计算代谢物浓度。代谢物浓度的差异是IDH突变的函数，1p/19q共同删除，使用Mann-WhitneyU检验确定生存状态。丙氨酸的浓度，谷氨酰胺,与具有IDH野生型的组织相比，具有IDH突变的神经胶质瘤组织中的谷氨酸和谷氨酸明显更低。此外,与完整的1p/19q相比，1p/19q共缺失的胶质瘤组织中的谷氨酸浓度显着降低。探索性分析显示，丙氨酸浓度随生存状态而显着变化。
结论：鉴于针对代谢失调的神经胶质瘤治疗的新兴景观，对神经胶质瘤分子亚型代谢改变的理解有所提高，包括具有IDH突变和1p/19q共缺失的那些，是治疗分层和个性化医疗的重要考虑因素。
目的：本研究旨在量化人神经胶质瘤组织中肿瘤代谢物的变化，作为IDH突变和1p/19q共缺失的函数。
结果：鉴定的人类神经胶质瘤组织和相关的临床数据是从埃默里大学Winship癌症研究所组织生物库获得的，来自14名患者（WHOII级，III,和IV；七个女性和七个男性）。使用600MHzBrukerAVANCEIIINMR光谱仪获得质子(1H)高分辨率幻角旋转(HR-MAS)核磁共振(NMR)光谱数据。使用LCModel计算代谢物浓度。代谢物浓度的差异是IDH突变的函数，1p/19q共同删除，使用Mann-WhitneyU检验确定生存状态。丙氨酸的浓度，谷氨酰胺,与具有IDH野生型的组织相比，具有IDH突变的神经胶质瘤组织中的谷氨酸和谷氨酸明显更低。此外,与完整的1p/19q相比，1p/19q共缺失的胶质瘤组织中的谷氨酸浓度显着降低。探索性分析显示，丙氨酸浓度随生存状态而显着变化。
结论：鉴于针对代谢失调的神经胶质瘤治疗的新兴景观，对神经胶质瘤分子亚型代谢改变的理解有所提高，包括具有IDH突变和1p/19q共缺失的那些，是治疗分层和个性化医疗的重要考虑因素。
