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异柠檬酸脱氢酶-1突变作为西波希米亚多形性胶质母细胞瘤患者的预后生物标志物

Isocitrate dehydrogenase-1 mutations as prognostic biomarker in glioblastoma multiforme patients in West Bohemia.

作者信息

Polivka J, Polivka J, Rohan V, Pesta M, Repik T, Pitule P, Topolcan O

机构信息

Department of Neurology, Faculty of Medicine in Pilsen, Charles University in Prague, Husova 3, 301 66 Pilsen, Czech Republic ; Faculty Hospital in Pilsen, Alej Svobody 80, 304 60 Pilsen, Czech Republic.

Department of Histology and Embryology and Biomedical Centre, Faculty of Medicine in Pilsen, Charles University in Prague, Husova 3, 301 66 Pilsen, Czech Republic.

出版信息

Biomed Res Int. 2014;2014:735659. doi: 10.1155/2014/735659. Epub 2014 Jan 9.

Abstract

INTRODUCTION

Glioblastoma multiforme (GBM) is the most malignant primary brain tumor in adults. Recent whole-genome studies revealed novel GBM prognostic biomarkers such as mutations in metabolic enzyme IDH-isocitrate dehydrogenases (IDH1 and IDH2). The distinctive mutation IDH1 R132H was uncovered to be a strong prognostic biomarker for glioma patients. We investigated the prognostic role of IDH1 R132H mutation in GBM patients in West Bohemia.

METHODS

The IDH1 R132H mutation was assessed by the RT-PCR in the tumor samples from 45 GBM patients treated in the Faculty Hospital in Pilsen and was correlated with the progression free and overall survival.

RESULTS

The IDH1 R132H mutation was identified in 20 from 44 GBM tumor samples (45.4%). The majority of mutated tumors were secondary GBMs (16 in 18, 89.9%). Low frequency of IDH1 mutations was observed in primary GBMs (4 in 26, 15.3%). Patients with IDH R132H mutation had longer PFS, 136 versus 51 days (P < 0.021, Wilcoxon), and OS, 270 versus 130 days (P < 0.024, Wilcoxon test).

SUMMARY

The prognostic value of IDH1 R132H mutation in GBM patients was verified. Patients with mutation had significantly longer PFS and OS than patients with wild-type IDH1 and suffered more likely from secondary GBMs.

摘要

引言

多形性胶质母细胞瘤(GBM)是成人中最恶性的原发性脑肿瘤。最近的全基因组研究揭示了新的GBM预后生物标志物,如代谢酶异柠檬酸脱氢酶(IDH1和IDH2)的突变。独特的IDH1 R132H突变被发现是胶质瘤患者的一个强大预后生物标志物。我们调查了IDH1 R132H突变在西波希米亚GBM患者中的预后作用。

方法

通过RT-PCR评估了在皮尔森市立医院接受治疗的45例GBM患者肿瘤样本中的IDH1 R132H突变,并将其与无进展生存期和总生存期相关联。

结果

在44例GBM肿瘤样本中的20例(45.4%)中鉴定出IDH1 R132H突变。大多数突变肿瘤为继发性GBM(18例中的16例,89.9%)。在原发性GBM中观察到IDH1突变的频率较低(26例中的4例,15.3%)。IDH R132H突变患者的无进展生存期更长,分别为136天和51天(P < 0.021,Wilcoxon检验),总生存期分别为270天和130天(P < 0.024,Wilcoxon检验)。

总结

IDH1 R132H突变在GBM患者中的预后价值得到了验证。与野生型IDH1患者相比,突变患者具有显著更长的无进展生存期和总生存期,并且更可能患有继发性GBM。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a41/3910481/85b071965e29/BMRI2014-735659.001.jpg

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