The elucidation of the molecule mechanism of the drug susceptibility in the chemotherapy for the oligodendroglioma

本研究对某肿瘤库的临床标本进行了染色体(1p、19q、10q、CDKN2N)缺失、TP53基因变异和EGFR、CDK4基因扩增的研究。许多伴有1P缺失的肿瘤是少突胶质瘤，约60%的少突胶质瘤中有1P缺失。同时伴随着19q的赤字。在无染色体1p缺陷的少突胶质细胞瘤中，可接受多种p53基因变异。其次，少突胶质细胞瘤化疗相关基因的药物敏感性。用微阵列(DNA芯片)对染色体1p进行了图谱分析，以用于推测位于染色体1p上的抑癌基因。因此，伴有1p单侧等位基因缺失的少突胶质细胞瘤的化疗敏感性较高。首次鉴定出染色体1p上故意改变的209个基因，其中123个基因被认为是抑癌基因，并利用基因芯片对星形细胞瘤和胶质母细胞瘤的基因表达谱进行分析，并与少突胶质细胞瘤进行比较分析。结果表明，在化疗敏感性较高的少突胶质细胞瘤中扩增的基因是神经元的基因簇。此外，还发现了一些星形细胞瘤或胶质母细胞瘤特有的基因。尽管有两例星形细胞瘤(WHO II级)的发现轮廓类似于胶质母细胞瘤(WHO IV级)，但这些病例的预后实际上很差，临床上也表现出类似胶质母细胞瘤的进展。因此，基因表达谱可以作为推测每个病例预后的工具。

This research investigated deficit of a chromosome (1p, 19q, 10q, CDKN2N), and variation of a gene TP53, and amplification of EGFR or CDK4 in many clinical samples of a tumor bank. Many of tumors accompanied by 1p deficit are oligodendroglioma, and it is in about 60% of the oligodendroglioma. It was simultaneously accompanied by the deficit of 19q. In the oligodendroglioma without the deficit of chromosome 1p, many gene variation of p53 was accepted.Next, the drug susceptibility in chemotherapy related gene of the oligodendroglioma. A profile analysis of chromosome 1p was performed by a microarray (DNA chip) for the purpose of the antioncogene identification assumed to be on chromosome 1p. Consequently, chemotherapy susceptibility is high among oligodendroglioma accompanied by the deficit of single-sided allele of 1p. For the first time 209 genes changing intentionally on chromosome 1p, and the 123 genes considered an antioncogene, were identified.Furthermore, for astrocytoma or glioblastoma gene expression profile analysis was performed by Gene chip, and comparison analysis with the oligodendroglioma was enforced. It became clear that the gene amplified in oligodendroglioma with high chemotherapy susceptibility was the gene cluster to a neuron. Moreover, some genes discovered characteristic of astrocytoma or the glioblastoma were also identified. Although, as for two examples of astrocytoma (WHO Grade II), the discovery profile resembled glioblastoma (WHO Grade IV), the prognosis of these cases was actually poor and, also clinically, showed progress like glioblastoma.Thus, a gene expression profile can serve as a tool which presumes the prognosis of each case.