Establishment of genetic diagnostics of brain tumors : Rapid diagnosis of mutation of p53 tumor suppressor gene.

本研究取得了如下重要成果：1）对星形细胞瘤的分析，在肿瘤材料和衍生细胞系匹配的情况下，证实了p53突变克隆的克隆扩增，支持体内脑肿瘤克隆进展的假设（Int J Cancer 1996）。2）在间变性星形细胞瘤和胶质母细胞瘤中应用该测定法证明了间变性星形细胞瘤中p53突变的比例较高（67%）。而不是胶质母细胞瘤（43%），这表明许多胶质母细胞瘤是通过p53非依赖性途径发展的，（Mol Carcinog 1997）。3）对胶质母细胞瘤患者的临床病理学参数的分析表明，p53突变是胶质母细胞瘤中更好的放射反应的标志物，这导致显著更长的生存期（Cancer Res 1998）4）将该测定应用于非星形细胞脑肿瘤表明，除了原发性恶性淋巴瘤之外，p53突变是罕见事件（Acta Neuropathol 1998）。5）对毛细胞型星形细胞瘤的分析表明，p53突变在这些肿瘤中是罕见的（Int J Cancer 1998）。6）通过总结上述结果，我们发表了几篇综述文章，包括一本书中的一章。

This project has yielded a considerable amount of results as follows.1) Analysis of astrocytomas, where matching tumor material and derived cell lines were available, demonstrated a clonal expansion of p53 mutated clone, supporting the hypothesis of clonal progression of brain tumors in vivo (Int J Cancer 1996).2) Application of the assay on anaplastic astrocytomas and glioblastomas demonstrated a higher ratio of p53 mutation in anaplastic astrocytomas (67%) than in glioblastomas (43%), indicating that that many glioblastomas develop by p53-independent pathways (Mol Carcinog 1997).3) Analysis of clinicopathological parameters in patients with glioblastomas demonstrated that p53 mutation is a marker for better radiation response in glioblastomas and this results in significantly longer survival (Cancer Res 1998)4) Application of the assay to non-astrocytic brain tumors demonstrated that p53 mutation is rare event except in primary malignant lymphomas (Acta Neuropathol 1998).5) Analysis of pilocytic astrocytomas demonstrated that p53 mutation is rare in these tumors (Int J Cancer 1998).6) By summarizing the above results, we have published severalreview articles, including a chapter in a book.