IDH1R132 mutation identified in one human melanoma metastasis, but not correlated with metastases to the brain
IDH1R132 mutation identified in one human melanoma metastasis, but not correlated with metastases to the brain
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DOI：
10.1016/j.bbrc.2010.06.125
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发表时间：
2010-07-30
影响因子：
3.1
通讯作者：
Yan, Hai
中科院分区：
文献类型：
--
作者：
Lopez, Giselle Y.;Reitman, Zachary J.;Yan, Hai
异柠檬酸脱氢酶1（IDH 1）和异柠檬酸脱氢酶2（IDH 2）是将异柠檬酸转化为α-酮戊二酸，同时将烟酰胺腺嘌呤二核苷酸磷酸（NADP +）还原为NADPH的酶。IDH 1/2最近被鉴定为在大比例的进行性神经胶质瘤中突变。这些突变发生在IDH 1（R132）或同源IDH 2（R172）。黑色素瘤与IDH 1/2突变的胶质瘤有一些共同的遗传特征，例如频繁的TP 53突变。我们试图测试黑色素瘤是否与IDH 1/2突变相关。分析了78份人黑素瘤样品的IDH 1（R132）和IDH 2（R172）突变状态。在一例转移至肺的人黑色素瘤中发现了体细胞杂合IDH 1 c.C394T（p.R132C）突变。在一个转移瘤中鉴定出这种突变后，我们试图检验以下假设：脑环境中的某些选择性压力可能特别有利于IDH 1/2突变的肿瘤细胞的细胞生长或存活，而不管原发肿瘤部位如何。为了解决这个问题，我们分析了IDH 1（R132）和IDH 2（R172）突变状态53转移性脑肿瘤，包括9个黑色素瘤转移。结果显示，所有样本均未发生突变。这种突变的缺乏表明IDH 1（R132）或IDH 2（R172）中的突变可能是以细胞谱系依赖性方式形成肿瘤所必需的，对于进行性神经胶质瘤中的突变具有特别强的选择压力;这也表明通常缺乏脑组织生长的特定选择压力。对IDH 1/2突变肿瘤细胞谱系的研究可能有助于阐明这些突变在脑肿瘤发展中的作用。(C)2010年爱思唯尔公司All rights reserved.
Isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) are enzymes which convert isocitrate to at-ketoglutarate while reducing nicotinamide adenine dinucleotide phosphate (NADP + to NADPH). IDH1/2 were recently identified as mutated in a large percentage of progressive gliomas. These mutations occur at IDH1(R132) or the homologous IDH2(R172). Melanomas share some genetic features with IDH 1/2-mutated gliomas, such as frequent TP53 mutation. We sought to test whether melanoma is associated with IDH1/2 mutations. Seventy-eight human melanoma samples were analyzed for IDH1(R132) and IDH2(R172) mutation status. A somatic, heterozygous IDH1 c.C394T (p.R132C) mutation was identified in one human melanoma metastasis to the lung. Having identified this mutation in one metastasis, we sought to test the hypothesis that certain selective pressures in the brain environment may specifically favor the cell growth or survival of tumor cells with mutations in IDH1/2, regardless of primary tumor site. To address this, we analyzed IDH1(R132) and IDH2(R172) mutation status 53 metastatic brain tumors, including nine melanoma metastases. Results revealed no mutations in any samples. This lack of mutations would suggest that mutations in IDH1(R132) or IDH2(R172) may be necessary for the formation of tumors in a cell-lineage dependent manner, with a particularly strong selective pressure for mutations in progressive gliomas; this also suggests the lack of a particular selective pressure for growth in brain tissue in general. Studies on the cell-lineages of tumors with IDH1/2 mutations may help clarify the role of these mutations in the development of brain tumors. (C) 2010 Elsevier Inc. All rights reserved.