Bouvier Corinne, Bartoli Catherine, Aguirre-Cruz Lucinda, Virard Isabelle, Colin Carole, Fernandez Carla, Gouvernet Joany, Figarella-Branger Dominique
Laboratoire des Interactions Neurone-Glie, Groupe Hospitalier Pitié-Salpétrière, Paris, France.
J Neurosurg. 2003 Aug;99(2):344-50. doi: 10.3171/jns.2003.99.2.0344.
Gliomas (astrocytic and oligodendroglial) are the most frequently occurring primary neoplasms in the central nervous system (CNS). Histological classification, which can be performed to distinguish astrocytomas from oligodendrogliomas, is essentially based on pathological features and has great prognostic and therapeutic value but lacks reproducibility. Specific markers of cell lineage, especially those f or oligodendrogliomas, are still lacking. The oligodendrocyte lineage (OLIG) genes, transcriptional factors of the basic helix-loop-helix family, have been recently identified in oligodendrocyte progenitor cells (OPCs) in the CNS of developing and adult rodents. Data from a few studies have shown in a small series of brain tumors that OLIG genes characterize oligodendrogliomas. To search for a differential expression of the OLIG genes in subgroups of brain tumors, the authors investigated OLIG1 and OLIG2 gene expression.
Using semiquantitative reverse transcription-polymerase chain reaction (RT-PCR), the authors analyzed a series of 89 tumors (71 astrocytic and oligodendroglial tumors, eight ependymomas, three medulloblastomas, four meningiomas, and three schwannomas) and normal human brain tissue samples. It was demonstrated that OLIG gene expression was largely limited to glial tumors, that is, astrocytomas and oligodendrogliomas. A very low level was detected in ependymomas, whereas other tumors lacked OLIG gene expression altogether. Surprisingly, OLIG1 and OLIG2 expressionwas not limited to oligodendroglial tumors, but was observed in astrocytic lesions as well, independent of tumor grade. Interestingly, these genes were expressed at the highest level in pilocytic astrocytomas according to semiquantitative RT-PCR results, which were confirmed on dot blot analysis. In situ hybridization showed that the OLIG2 gene was expressed by tumor cells in pilocytic astrocytomas as well as those in oligodendrogliomas.
The OLIG genes are additional markers shared by all gliomas andOPCs. These markers may help to classify gliomas, to improve understanding of their histogenesis, and to identify new therapeutic targets.
神经胶质瘤(星形细胞瘤和少突胶质细胞瘤)是中枢神经系统(CNS)中最常见的原发性肿瘤。组织学分类可用于区分星形细胞瘤和少突胶质细胞瘤,其本质上基于病理特征,具有重要的预后和治疗价值,但缺乏可重复性。细胞谱系的特异性标志物,尤其是少突胶质细胞瘤的标志物,仍然缺乏。少突胶质细胞谱系(OLIG)基因是碱性螺旋-环-螺旋家族的转录因子,最近在发育中和成年啮齿动物中枢神经系统的少突胶质前体细胞(OPC)中被鉴定出来。一些研究的数据显示,在一小系列脑肿瘤中,OLIG基因可表征少突胶质细胞瘤。为了寻找脑肿瘤亚组中OLIG基因的差异表达,作者研究了OLIG1和OLIG2基因的表达。
作者使用半定量逆转录-聚合酶链反应(RT-PCR)分析了一系列89个肿瘤(71个星形细胞瘤和少突胶质细胞瘤、8个室管膜瘤、3个髓母细胞瘤、4个脑膜瘤和3个神经鞘瘤)以及正常人类脑组织样本。结果表明,OLIG基因表达在很大程度上限于神经胶质瘤,即星形细胞瘤和少突胶质细胞瘤。在室管膜瘤中检测到极低水平,而其他肿瘤则完全缺乏OLIG基因表达。令人惊讶的是,OLIG1和OLIG2的表达并不限于少突胶质细胞瘤,在星形细胞病变中也可观察到,且与肿瘤分级无关。有趣的是,根据半定量RT-PCR结果,这些基因在毛细胞型星形细胞瘤中表达水平最高,这在斑点印迹分析中得到了证实。原位杂交显示,OLIG2基因在毛细胞型星形细胞瘤以及少突胶质细胞瘤的肿瘤细胞中表达。
OLIG基因是所有神经胶质瘤和OPC共有的额外标志物。这些标志物可能有助于神经胶质瘤的分类,增进对其组织发生的理解,并识别新的治疗靶点。