Prediction of genetic subgroups in adult supra tentorial gliomas by pre- and intraoperative parameters
Prediction of genetic subgroups in adult supra tentorial gliomas by pre- and intraoperative parameters
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DOI：
10.1007/s11060-016-2313-8
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发表时间：
2017-01-01
影响因子：
3.9
通讯作者：
Hirose, Yuichi
中科院分区：
文献类型：
--
作者：
Nakae, Shunsuke;Murayama, Kazuhiro;Hirose, Yuichi
神经肿瘤学的最新进展证实了基因诊断在胶质瘤中的重要性。我们之前通过桑格测序对成人幕上胶质瘤的IDH 1/2和TP 53突变进行了研究，并报道了基于PCR的序列分析将胶质瘤分为三个与患者预后密切相关的遗传亚组：IDH突变型胶质瘤无TP 53突变，IDH和TP 53突变型胶质瘤，以及IDH野生型胶质瘤。此外，该分析与患者预后密切相关。为了在初次手术前预测基因亚组，我们回顾性研究了术前CT和MRI的影像学资料，包括MR波谱（MRS），并评估了阳性5-氨基乙酰丙酸（5-ALA）荧光作为术中因素。我们随后比较了这些因素，以区分每个遗传亚组。诊断时的年龄、肿瘤位置、钆增强、5-ALA荧光和MRS所示的几种肿瘤代谢物如肌醇（肌醇/总胆碱）或脂质20等多种因素是区分IDH突变型和野生型的统计学显著因素，表明这两种亚型具有完全不同的特征。相反，只有钙化、偏侧性和脂质13（脂质13/总胆碱）是区分IDH突变型胶质瘤中TP 53野生型和突变型的统计学显著参数。在这项研究中，我们检测了几个术前和术中因素，使我们能够预测成人幕上胶质瘤的遗传亚群，并澄清了MRS定量的lipid 13是区分IDH突变型胶质瘤中TP 53野生型和突变型的关键肿瘤代谢物。这些结果表明，在胶质瘤的发生过程中，每个基因亚型选择不同的脂质合成途径。
Recent progress in neuro-oncology has validated the significance of genetic diagnosis in gliomas. We previously investigated IDH1/2 and TP53 mutations via Sanger sequencing for adult supratentorial gliomas and reported that PCR-based sequence analysis classified gliomas into three genetic subgroups that have a strong association with patient prognosis: IDH mutant gliomas without TP53 mutations, IDH and TP53 mutant gliomas, and IDH wild-type gliomas. Furthermore, this analysis had a strong association with patient prognosis. To predict genetic subgroups prior to initial surgery, we retrospectively investigated preoperative radiological data using CT and MRI, including MR spectroscopy (MRS), and evaluated positive 5-aminolevulinic acid (5-ALA) fluorescence as an intraoperative factor. We subsequently compared these factors to differentiate each genetic subgroup. Multiple factors such as age at diagnosis, tumor location, gadolinium enhancement, 5-ALA fluorescence, and several tumor metabolites according to MRS, such as myo-inositol (myo-inositol/total choline) or lipid20, were statistically significant factors for differentiating IDH mutant and wild-type, suggesting that these two subtypes have totally distinct characteristics. In contrast, only calcification, laterality, and lipid13 (lipid13/total Choline) were statistically significant parameters for differentiating TP53 wild-type and mutant in IDH mutant gliomas. In this study, we detected several pre- and intraoperative factors that enabled us to predict genetic subgroups for adult supratentorial gliomas and clarified that lipid13 quantified by MRS is the key tumor metabolite that differentiates TP53 wild-type and mutant in IDH mutant gliomas. These results suggested that each genetic subtype in gliomas selects the distinct lipid synthesis pathways in the process of tumorigenesis.