Ohka Fumiharu, Yamamichi Akane, Kurimoto Michihiro, Motomura Kazuya, Tanahashi Kuniaki, Suzuki Hiromichi, Aoki Kosuke, Deguchi Shoichi, Chalise Lushun, Hirano Masaki, Kato Akira, Nishimura Yusuke, Hara Masahito, Kato Yukinari, Wakabayashi Toshihiko, Natsume Atsushi
Department of Neurosurgery, Nagoya University, Nagoya, Japan.
Department of Neurosurgery, Mie University, Tsu, Japan.
Brain Tumor Pathol. 2017 Apr;34(2):91-97. doi: 10.1007/s10014-017-0281-0. Epub 2017 Mar 28.
IDH1 gene mutation has been demonstrated to be an oncogenic driver in a majority of lower-grade gliomas (LGGs). In contrast to other central nervous neoplasms and normal brain tissue without IDH1 mutation, almost 80% of LGGs exhibit IDH1 mutation. Therefore, expeditious detection of IDH1 mutation is useful, not only for intraoperative diagnosis of these gliomas but also for determination of the border between the tumor and normal brain tissue. In this study, we established a rapid genotyping assay with a simple DNA extraction method, involving only incubation of the tumor specimen with Tris-EDTA buffer, which can be easily performed in an operating room. In all 11 tested cases, we could identify the IDH1 status within 90-100 min intraoperatively. In a case of anaplastic astrocytoma, IDH-mutant, we could detect the tumor border by IDH1 profiling. In addition, with this assay, we could detect IDH1 mutation using cell-free tumor DNA derived from cerebrospinal fluid in a case of glioblastoma, IDH-mutant. Considering that clinical trials of mutated IDH1 inhibitors are ongoing, less-invasive intraoperative IDH1 gene profiling might be useful for decision making of the overall treatment strategy of LGGs. Our assay might be a useful tool for precision medicine and surgery of IDH1-mutant gliomas.
IDH1基因突变已被证明是大多数低级别胶质瘤（LGG）的致癌驱动因素。与其他中枢神经系统肿瘤和无IDH1突变的正常脑组织相比，近80%的LGG存在IDH1突变。因此，快速检测IDH1突变不仅有助于这些胶质瘤的术中诊断，还有助于确定肿瘤与正常脑组织之间的边界。在本研究中，我们建立了一种快速基因分型检测方法，采用简单的DNA提取方法，仅将肿瘤标本与Tris-EDTA缓冲液孵育，这可以在手术室轻松完成。在所有11例测试病例中，我们能够在术中90-100分钟内确定IDH1状态。在一例间变性星形细胞瘤（IDH突变型）病例中，我们能够通过IDH1分析检测肿瘤边界。此外，通过该检测方法，我们能够在一例胶质母细胞瘤（IDH突变型）病例中使用源自脑脊液的游离肿瘤DNA检测IDH1突变。鉴于针对突变型IDH1抑制剂的临床试验正在进行，侵入性较小的术中IDH1基因分析可能有助于LGG整体治疗策略的决策。我们的检测方法可能是IDH1突变型胶质瘤精准医学和手术的有用工具。
