Institute of Neurology (Edinger Institute), Goethe University, Frankfurt, Germany.
Neuropathol Appl Neurobiol. 2014 Feb;40(2):205-16. doi: 10.1111/nan.12088.
The Far Upstream Element [FUSE] Binding Protein 1 (FUBP1) regulates target genes, such as the cell cycle regulators MYC and p21. FUBP1 is up-regulated in many tumours and acts as an oncoprotein by stimulating proliferation and inhibiting apoptosis. Recently, FUBP1 mutations were identified in approximately 15% of oligodendrogliomas. To date, all reported FUBP1 mutations have been predicted to inactivate FUBP1, which suggests that in contrast to most other tumours FUBP1 may act as a tumour suppressor in oligodendrogliomas.
As no data are currently available concerning FUBP1 protein levels in gliomas, we examined the FUBP1 expression profiles of human glial tumours by immunohistochemistry and immunofluorescence. We analysed FUBP1 expression related to morphological differentiation, IDH1 and FUBP1 mutation status, 1p/19q loss of heterozygosity (LOH) as well as proliferation rate.
Our findings demonstrate that FUBP1 expression levels are increased in all glioma subtypes as compared with normal central nervous system (CNS) control tissue and are associated with increased proliferation. In contrast, FUBP1 immunonegativity predicted FUBP1 mutation with a sensitivity of 100% and a specificity of 90% in our cohort and was associated with oligodendroglial differentiation, IDH1 mutation and 1p/19q loss of heterozygosity (LOH). Using this approach, we detected a to-date undescribed FUBP1 mutation in an oligodendroglioma.
In summary, our data indicate an association between of FUBP1 expression and proliferation in gliomas. Furthermore, our findings present FUBP1 immunohistochemical analysis as a helpful additional tool for neuropathological glioma diagnostics predicting FUBP1 mutation.
远上游元件（FUSE）结合蛋白 1（FUBP1）调节靶基因，如细胞周期调节剂 MYC 和 p21。FUBP1 在许多肿瘤中上调，并通过刺激增殖和抑制凋亡发挥癌蛋白作用。最近，在大约 15%的少突胶质细胞瘤中鉴定出 FUBP1 突变。迄今为止，所有报道的 FUBP1 突变都被预测会使 FUBP1 失活，这表明与大多数其他肿瘤相反，FUBP1 可能在少突胶质细胞瘤中作为肿瘤抑制因子发挥作用。
由于目前尚无关于神经胶质瘤中 FUBP1 蛋白水平的数据，我们通过免疫组织化学和免疫荧光法检查了人类神经胶质瘤的 FUBP1 表达谱。我们分析了 FUBP1 表达与形态分化、IDH1 和 FUBP1 突变状态、1p/19q 杂合性丢失（LOH）以及增殖率的关系。
我们的研究结果表明，与正常中枢神经系统（CNS）对照组织相比，所有神经胶质瘤亚型的 FUBP1 表达水平均升高，并与增殖增加相关。相反，FUBP1 免疫阴性预测 FUBP1 突变在我们的队列中具有 100%的敏感性和 90%的特异性，并且与少突胶质细胞分化、IDH1 突变和 1p/19q 杂合性丢失（LOH）相关。使用这种方法，我们在一个少突胶质细胞瘤中检测到了一个迄今为止尚未描述的 FUBP1 突变。
总之，我们的数据表明 FUBP1 表达与神经胶质瘤的增殖之间存在关联。此外，我们的研究结果表明，FUBP1 免疫组织化学分析可作为神经病理胶质瘤诊断的有用辅助工具，预测 FUBP1 突变。
