Type and frequency of IDH1 and IDH2 mutations are related to astrocytic and oligodendroglial differentiation and age: a study of 1,010 diffuse gliomas
Type and frequency of IDH1 and IDH2 mutations are related to astrocytic and oligodendroglial differentiation and age: a study of 1,010 diffuse gliomas
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DOI：
10.1007/s00401-009-0561-9
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发表时间：
2009-10-01
影响因子：
12.7
通讯作者：
von Deimling, Andreas
中科院分区：
文献类型：
--
作者：
Hartmann, Christian;Meyer, Jochen;von Deimling, Andreas
在大多数星形胶质细胞瘤，寡胶质细胞瘤和寡胶质细胞瘤中，已经显示了编码胞质NADP+依赖性异位酸脱氢酶的IDH1基因中的体细胞突变。编码线粒体NADP+依赖性的异戊二酸脱氢酶的IDH2在这些肿瘤中也被突变，尽管频率低得多。初步数据表明，IDH1突变对预后的重要性表明，具有肿瘤性IDH1突变的型变性星形瘤，少突胶质瘤和少突腹膜的患者似乎比没有这种突变的患者的毛病表现要好得多。为了确定突变类型及其频率，我们检查了1,010个弥漫性神经胶质瘤。我们检测到716个IDH1突变和31个IDH2突变。我们在227个差异的星形胶质细胞瘤中发现了165个IDH1（72.7％）和2个IDH2突变（0.9％），其中II级，146 IDH1（64.0％）和228个阶层星形星形胶质细胞瘤中的228级III，105 iii，1052.0（82.0）（82.0）（82.0）（82.0）（82.0）（82.0）中的146 IDH1（64.0％）和2个IDH2突变（0.9％） ％）和6个IDH2突变（4.7％）中的128个寡头瘤WHO II级，121 IDH1（69.5％）和94个IDH2突变（5.2％），174个偏型寡聚胶质瘤WHO III级，62 IDH1（81.6％）（81.6％）和1个IDH2突变（1.3％） 177中的66.1％）和11个IDH2突变（6.2％） III级的那内性寡构瘤。我们报告了这些神经胶质瘤中IDH1和IDH2突变的逆关联，以及肿瘤实体内突变类型的非随机分布。 R132C类型的IDH1突变与星形胶质细胞瘤密切相关，而IDH2突变主要发生在寡头肿瘤中。此外，携带IDH1突变的变性神经胶质瘤的患者平均比没有这些改变的患者小6岁。
Somatic mutations in the IDH1 gene encoding cytosolic NADP+-dependent isocitrate dehydrogenase have been shown in the majority of astrocytomas, oligodendrogliomas and oligoastrocytomas of WHO grades II and III. IDH2 encoding mitochondrial NADP+-dependent isocitrate dehydrogenase is also mutated in these tumors, albeit at much lower frequencies. Preliminary data suggest an importance of IDH1 mutation for prognosis showing that patients with anaplastic astrocytomas, oligodendrogliomas and oligoastrocytomas harboring IDH1 mutations seem to fare much better than patients without this mutation in their tumors. To determine mutation types and their frequencies, we examined 1,010 diffuse gliomas. We detected 716 IDH1 mutations and 31 IDH2 mutations. We found 165 IDH1 (72.7%) and 2 IDH2 mutations (0.9%) in 227 diffuse astrocytomas WHO grade II, 146 IDH1 (64.0%) and 2 IDH2 mutations (0.9%) in 228 anaplastic astrocytomas WHO grade III, 105 IDH1 (82.0%) and 6 IDH2 mutations (4.7%) in 128 oligodendrogliomas WHO grade II, 121 IDH1 (69.5%) and 9 IDH2 mutations (5.2%) in 174 anaplastic oligodendrogliomas WHO grade III, 62 IDH1 (81.6%) and 1 IDH2 mutations (1.3%) in 76 oligoastrocytomas WHO grade II and 117 IDH1 (66.1%) and 11 IDH2 mutations (6.2%) in 177 anaplastic oligoastrocytomas WHO grade III. We report on an inverse association of IDH1 and IDH2 mutations in these gliomas and a non-random distribution of the mutation types within the tumor entities. IDH1 mutations of the R132C type are strongly associated with astrocytoma, while IDH2 mutations predominantly occur in oligodendroglial tumors. In addition, patients with anaplastic glioma harboring IDH1 mutations were on average 6 years younger than those without these alterations.