The CASPR2 cell adhesion molecule functions as a tumor suppressor gene in glioma
The CASPR2 cell adhesion molecule functions as a tumor suppressor gene in glioma
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DOI：
10.1038/onc.2010.342
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发表时间：
2010-11-01
期刊：
影响因子：
8
通讯作者：
French, P. J.
中科院分区：
文献类型：
--
作者：
Bralten, L. B. C.;Gravendeel, A. M.;French, P. J.
基因组易位与癌症有关。在这项研究中，我们进行了一个屏幕上的基因易位在胶质瘤的基础上外显子水平的表达谱。我们发现了编码细胞粘附分子的接触素相关蛋白样2（CASPR 2）基因的易位。CASPR 2 mRNA与表达的序列标签融合，该序列标签可能是核受体辅激活因子1基因的一部分。尽管mRNA表达水平高，但未检测到CASPR 2融合蛋白。在一组25例胶质母细胞瘤和22例少突胶质细胞瘤中，突变分析确定了另外两个CASPR 2基因发生遗传改变的样本，所有三个确定的遗传改变都可能降低CASPR 2蛋白表达水平。CASPR 2基因的甲基化也在胶质瘤和胶质瘤细胞系中观察到。CASPR 2过表达的细胞显示增殖率降低，可能是因为凋亡增加。CASPR 2 mRNA的高表达水平与患者的生存率呈正相关，是一个独立的预后因素。这些结果表明CASPR 2在胶质瘤中起肿瘤抑制基因的作用。Oncogene（2010）29，6138-6148; doi：10.1038/onc.2010.342; 2010年8月16日在线发表
Genomic translocations have been implicated in cancer. In this study, we performed a screen for genetic translocations in gliomas based on exon-level expression profiles. We identified a translocation in the contactin-associated protein-like 2 (CASPR2) gene, encoding a cell adhesion molecule. CASPR2 mRNA was fused to an expressed sequence tag that likely is part of the nuclear receptor coactivator 1 gene. Despite high mRNA expression levels, no CASPR2 fusion protein was detected. In a set of 25 glioblastomas and 22 oligodendrogliomas, mutation analysis identified two additional samples with genetic alterations in the CASPR2 gene and all three identified genetic alterations are likely to reduce CASPR2 protein expression levels. Methylation of the CASPR2 gene was also observed in gliomas and glioma cell lines. CASPR2-overexpressing cells showed decreased proliferation rates, likely because of an increase in apoptosis. Moreover, high CASPR2 mRNA expression level is positively correlated with survival and is an independent prognostic factor. These results indicate that CASPR2 acts as a tumor suppressor gene in glioma. Oncogene (2010) 29, 6138-6148; doi:10.1038/onc.2010.342; published online 16 August 2010