激活Akt PTEN和独立的CTMP肿瘤抑制基因的突变epilepsy-associated泰勒型局灶性皮质发育不良。
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锡克V,主要M,恩格斯G, Spitoni年代,科赫,Elger CE、西蒙·M Knobbe C, Blumcke我,贝克尔AJ
激活Akt PTEN和独立的CTMP肿瘤抑制基因的突变epilepsy-associated泰勒型局灶性皮质发育不良。
Acta Neuropathol。2006年12月,112(6):715 - 25所示。Epub 2006年9月30日。
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17013611 (在PubMed]
- 文摘
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局灶性皮质发育不良(FCD)泰勒式气球细胞(FCD (IIb))经常观察pharmacoresistant焦的癫痫病患者的活检标本。FCD (IIb)的分子发病机制,缺乏家庭继承,只有知之甚少。由于其高度分化,malformative性质和glioneuronal表型,FCD (IIb)分享神经病理特征等家族性疾病的病变观察结节患者出现在常染色体显性复杂结节性硬化症(TSC),与TSC1或TSC2基因突变有关,和发育异常的gangliocytomas Cowden小脑发现的疾病。当前数据表示不同的等位变异TSC1积累在FCD (IIb)。TSC1代表一个肿瘤抑制磷脂酰肌醇的操作3-kinase (PI3K) /胰岛素通路。肿瘤抑制基因PTEN突变Cowden疾病。也像PTEN、羧基末端调制器蛋白(CTMP)调节PI3K-pathway信号,通过抑制一种蛋白激酶/ PKB,激酶灭活TSC1 / TSC2复杂。在这里,我们分析了改变的一种蛋白激酶,PTEN与CTMP与胰岛素信号传导相关的上游TSC1 / TSC2 FCD (IIb)。免疫组织化学与磷酸化抗体一种蛋白激酶(phospho-Akt;爵士473年FCD) (IIb) (n = 23)显示强劲phospho-Akt表达发育异常的FCD (IIb)组件。 We have further studied sequence alterations of PTEN (n=34 FCD(IIb)) and CTMP (n=20 FCD(IIb)) by laser microdissection/single-strand conformation polymorphism analysis. We observed a somatic mutation in an FCD(IIb), i.e., amino-acid exchange at nucleotide position 834 (PTEN cDNA, GenBank AH007803.1) in exon 8 with replacement of phenylalanine by leucine (F278L). We also found several silent polymorphisms of PTEN in exon 2 and exon 8 as well as silent and coding polymorphisms but no mutations in CTMP. No loss of heterozygosity in FCD(IIb) (n=6) at 10q23 was observed. To our knowledge, we here report on the first somatic mutation of a tumor-suppressor gene, i.e., PTEN, in FCD(IIb). However, our study also demonstrates that mutational alterations of PTEN and CTMP do not play major pathogenetic roles for activation of Akt in FCD(IIb). Future studies need to determine the origin of insulin pathway activation upstream of TSC1/TSC2 in FCD(IIb).