Department of Chemistry, Purdue University, West Lafayette, IN, 47907, USA.
Department of Precision Instrument, Tsinghua University, Beijing, 100084, China.
Anal Bioanal Chem. 2019 Mar;411(8):1503-1508. doi: 10.1007/s00216-019-01632-5. Epub 2019 Feb 2.
Isocitrate dehydrogenase (IDH) I and II mutations in gliomas cause an abnormal accumulation of 2-hydroxyglutarate (2-HG) in these tumor cells. These mutations have potential prognostic value in that knowledge of the mutation status can lead to improved surgical resection. Information on mutation status obtained by immunohistochemistry or genomic analysis is not available during surgery. We report a rapid extraction nanoelectrospray ionization (nESI) method of determining 2-HG. This should allow the determination of IDH mutation status to be performed intraoperatively, within minutes, using a miniature mass spectrometer. This study demonstrates that the combination of tandem mass spectrometry with low-resolution mass spectrometry allows this analysis to be performed with confidence. Graphical Abstract.
在神经胶质瘤中,异柠檬酸脱氢酶(IDH)I 和 II 的突变导致这些肿瘤细胞中 2-羟戊二酸(2-HG)的异常积累。这些突变在预测预后方面具有潜在的价值,因为了解突变状态可以导致更好的手术切除。在手术过程中,免疫组织化学或基因组分析获得的突变状态信息不可用。我们报告了一种快速提取纳米电喷雾电离(nESI)方法来测定 2-HG。这应该允许使用微型质谱仪在几分钟内进行术中 IDH 突变状态的测定。本研究表明,串联质谱法与低分辨率质谱法相结合,可以确保这种分析的准确性。