Neurosurgery, University Hospital Carl Gustav Carus, TU Dresden, Fetscherstr. 74, 01307, Dresden, Germany.
Department of Anesthesiology and Intensive Care Medicine, Faculty of Medicine, Clinical Sensoring and Monitoring, TU Dresden, Fetscherstr. 74, 01307, Dresden, Germany.
J Neurooncol. 2018 Sep;139(2):261-268. doi: 10.1007/s11060-018-2883-8. Epub 2018 May 14.
Mutations in the isocytrate dehydrogenase 1 (IDH1) gene are early genetic events in glioma pathogenesis and cause profound metabolic changes. Because this genotype is found in virtually every tumor cell, therapies targeting mutant IDH1 protein are being developed. The intraoperative administration of those therapies would require fast technologies for the determination of IDH1 genotype. As of today, there is no such diagnostic test available. Recently, infrared spectroscopy was shown to bridge this gap. Here, we tested Raman spectroscopy for analysis of IDH1 genotype in glioma, which constitutes an alternative contact-free technique with the potential of being applicable in situ.
Human glioma samples (n = 36) were obtained during surgery and cryosections were prepared. IDH1 mutations were assessed using DNA sequencing and 100 Raman spectra were obtained for each sample.
Analysis of Raman spectra revealed increased intensities in spectral bands related to DNA in IDH1 mutant glioma while bands assigned to molecular vibrations of lipids were significantly decreased. Moreover, intensities of Raman bands assigned to proteins differed in IDH1 mutant and IDH1 wild-type glioma, suggesting alterations in the protein profile. The selection of five bands (498, 826, 1003, 1174 and 1337 cm) allowed the classification of Raman spectra according to IDH1 genotype with a correct rate of 89%.
Raman spectroscopy constitutes a simple, rapid and safe procedure for determination of the IDH1 mutation that shows great promise for clinically relevant in situ diagnostics.
异柠檬酸脱氢酶 1（IDH1）基因突变是胶质瘤发病过程中的早期遗传事件，导致代谢发生深刻变化。由于这种基因型几乎存在于每个肿瘤细胞中，因此正在开发针对突变 IDH1 蛋白的治疗方法。这些治疗方法的术中给药需要快速确定 IDH1 基因型的技术。到目前为止，还没有这样的诊断测试。最近，红外光谱被证明可以弥补这一空白。在这里，我们测试了拉曼光谱在胶质瘤 IDH1 基因型分析中的应用，这是一种替代的非接触技术，具有潜在的原位应用能力。
在手术中获取人类胶质瘤样本（n=36）并制备冷冻切片。使用 DNA 测序评估 IDH1 突变，每个样本获得 100 个拉曼光谱。
拉曼光谱分析显示，IDH1 突变型胶质瘤中与 DNA 相关的光谱带强度增加，而分配给脂质分子振动的带强度显著降低。此外，IDH1 突变型和 IDH1 野生型胶质瘤中分配给蛋白质的拉曼带强度不同，表明蛋白质谱发生了改变。选择五个带（498、826、1003、1174 和 1337 cm）允许根据 IDH1 基因型对拉曼光谱进行分类，准确率为 89%。
拉曼光谱是一种简单、快速和安全的 IDH1 突变检测方法，对于临床相关的原位诊断具有广阔的前景。
