Balss Jörg, Meyer Jochen, Mueller Wolf, Korshunov Andrey, Hartmann Christian, von Deimling Andreas
Clinical Cooperation Unit Neuropathology G380, German Cancer Research Center, 69120, Heidelberg, Germany.
Acta Neuropathol. 2008 Dec;116(6):597-602. doi: 10.1007/s00401-008-0455-2. Epub 2008 Nov 5.
A recent study reported on mutations in the active site of the isocitrate dehydrogenase (IDH1) gene in 12% of glioblastomas. All mutations detected resulted in an amino acid exchange in position 132. We analyzed the genomic region spanning wild type R132 of IDH1 by direct sequencing in 685 brain tumors including 41 pilocytic astrocytomas, 12 subependymal giant cell astrocytomas, 7 pleomorphic xanthoastrocytomas, 93 diffuse astrocytomas, 120 adult glioblastomas, 14 pediatric glioblastomas, 105 oligodendrogliomas, 83 oligoastrocytomas, 31 ependymomas, 58 medulloblastomas, 9 supratentorial primitive neuroectodermal tumors, 17 schwannomas, 72 meningiomas and 23 pituitary adenomas. A total of 221 somatic IDH1 mutations were detected and the highest frequencies occurred in diffuse astrocytomas (68%), oligodendrogliomas (69%), oligoastrocytomas (78%) and secondary glioblastomas (88%). Primary glioblastomas and other entities were characterized by a low frequency or absence of mutations in amino acid position 132 of IDH1. The very high frequency of IDH1 mutations in WHO grade II astrocytic and oligodendroglial gliomas suggests a role in early tumor development.
最近一项研究报告称，在12%的胶质母细胞瘤中，异柠檬酸脱氢酶（IDH1）基因的活性位点发生了突变。所有检测到的突变均导致第132位氨基酸发生交换。我们通过直接测序分析了685例脑肿瘤中IDH1野生型R132所在的基因组区域，这些脑肿瘤包括41例毛细胞型星形细胞瘤、12例室管膜下巨细胞星形细胞瘤、7例多形性黄色星形细胞瘤、93例弥漫性星形细胞瘤、120例成人胶质母细胞瘤、14例儿童胶质母细胞瘤、105例少突胶质细胞瘤、83例少突星形细胞瘤、31例室管膜瘤、58例髓母细胞瘤、9例幕上原始神经外胚层肿瘤、17例神经鞘瘤、72例脑膜瘤和23例垂体腺瘤。共检测到221个IDH1体细胞突变，最高频率出现在弥漫性星形细胞瘤（68%）、少突胶质细胞瘤（69%）、少突星形细胞瘤（78%）和继发性胶质母细胞瘤（88%）中。原发性胶质母细胞瘤和其他实体瘤的特征是IDH1第132位氨基酸的突变频率较低或无突变。IDH1突变在世界卫生组织II级星形细胞和少突胶质细胞胶质瘤中的极高频率表明其在肿瘤早期发展中起作用。
