Detection of 2-hydroxyglutarate in IDH-mutated glioma patients by in vivo spectral-editing and 2D correlation magnetic resonance spectroscopy.
Detection of 2-hydroxyglutarate in IDH-mutated glioma patients by in vivo spectral-editing and 2D correlation magnetic resonance spectroscopy.
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DOI：
10.1126/scitranslmed.3002693
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发表时间：
2012-01-11
影响因子：
17.1
通讯作者：
Sorensen AG
中科院分区：
文献类型：
--
作者：
Andronesi OC;Kim GS;Gerstner E;Batchelor T;Tzika AA;Fantin VR;Vander Heiden MG;Sorensen AG
异柠檬酸脱氢酶1 （IDH1）中精氨酸132 （R132）的突变存在于高达86%的II级和III级胶质瘤和继发性胶质母细胞瘤中。IDH1的R132突变导致代谢物2-羟基戊二酸（2HG）的过量产生，这可以用作该神经胶质瘤亚群的生物标志物。在这里，我们使用优化的光谱编辑和二维（2D）相关磁共振波谱（MRS）方法，在IDH1突变的胶质瘤患者中明确地检测2HG。相比之下，由于2HG和化学上相似的脑代谢物（如谷氨酸和谷氨酰胺）的光谱重叠，传统的1D MR光谱拟合可能会产生假阳性读数。通过对另一组胶质瘤活检样本进行二维高分辨率魔角旋转MRS，也发现了2HG。通过体内或离体磁共振检测2HG，可以对临床上重要的人类胶质瘤亚群进行详细的分子表征。这对诊断和监测针对IDH突变的治疗具有重要意义。
Mutations of arginine 132 (R132) in the enzyme isocitrate dehydrogenase-1 (IDH1) are present in up to 86% of grade II and III gliomas and secondary glioblastoma. R132 mutations in IDH1 result in excess production of the metabolite 2-hydroxyglutarate (2HG), which could be used as a biomarker for this subset of gliomas. Here, we use optimized spectral-editing and two-dimensional (2D) correlation magnetic resonance spectroscopy (MRS) methods to unambiguously detect 2HG non-invasively in glioma patients with IDH1 mutations. By comparison, fitting of conventional 1D MR spectra can provide false-positive readouts owing to spectral overlap of 2HG and chemically similar brain metabolites, such as glutamate and glutamine. 2HG has been found also by 2D high-resolution magic angle spinning MRS performed ex vivo on a separate set of glioma biopsy samples. 2HG detection by in vivo or ex vivo MRS enabled detailed molecular characterization of a clinically important subset of human gliomas. This has implications for diagnosis as well as monitoring of treatments targeting IDH mutations.
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影响因子：
64.8
作者：
通讯作者：
--
影响因子：
2.2
作者：
Lin, YY;Hodgkinson, P;Pines, A
通讯作者：
Pines, A
影响因子：
2.9
作者：
Near, Jamie;Simpson, Robin;Jezzard, Peter
通讯作者：
Jezzard, Peter
影响因子：
2.9
作者：
Martínez-Bisbal, MC;Martí-Bonmatí, L;Celda, B
通讯作者：
Celda, B
DOI：
10.1126/science.1164382
发表时间：
2008-09-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Parsons DW;Jones S;Zhang X;Lin JC;Leary RJ;Angenendt P;Mankoo P;Carter H;Siu IM;Gallia GL;Olivi A;McLendon R;Rasheed BA;Keir S;Nikolskaya T;Nikolsky Y;Busam DA;Tekleab H;Diaz LA Jr;Hartigan J;Smith DR;Strausberg RL;Marie SK;Shinjo SM;Yan H;Riggins GJ;Bigner DD;Karchin R;Papadopoulos N;Parmigiani G;Vogelstein B;Velculescu VE;Kinzler KW
通讯作者：
Kinzler KW