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

脑肿瘤基因诊断的建立：p53抑癌基因突变的快速诊断。

• 批准号: 08457355
• 负责人: SAWAMURA Yutaka
• 金额: $ 4.35万
• 依托单位: HOKKAIDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08457355/
• 关键词: p53; genetic diagnosis; yeast p53 functional assay; astrocytoma; glioblastoma; brain tumor; prognosis; gene diagnosis

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.

本项目取得了大量成果如下：1)对星形细胞瘤的分析，在可获得匹配的肿瘤材料和衍生细胞系的情况下，证实了p53突变克隆的克隆性扩张，支持了体内脑肿瘤克隆进展的假说(Int J Cancer 1996)。2)对间变性星形细胞瘤和胶质母细胞瘤的检测表明，间变性星形细胞瘤(67%)的p53突变率(67%)高于胶质母细胞瘤(43%)。3)对胶质母细胞瘤患者的临床病理参数分析表明，P53突变是胶质母细胞瘤更好的辐射反应的标志，这导致显著的更长的生存(癌症RES 1998)4)应用于非星形细胞脑肿瘤的检测表明，P53突变是罕见的事件，除了在原发的恶性淋巴瘤(神经病理学学报1998)。5)毛细胞性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癌症1998)。6)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。

项目成果

Nozaki M: "Rare occurrence of p53 gene mutation in non-astrocytic brain tumors-Reappraisal by yeast functional assay." Acta Neuropathologica. 95. 291-296 (1998)

Nozaki M：“非星形细胞脑肿瘤中罕见的 p53 基因突变 - 通过酵母功能测定进行重新评估。”

Nozaki M: "Expression study of oncogenic molecules in primary central nervous system lymphomas in immunocompetent patients." Acta Neuropathologica. 95. 505-510 (1998)

Nozaki M：“免疫功能正常患者原发性中枢神经系统淋巴瘤中致癌分子的表达研究。”

Nozaki M,et al.: "Rare occurrence of p53 gene mutation in non-astrocytic brain tumors-Reappraisal by yeast functional assay." Acta Neuropathol. 95. 291-296 (1998)

Nozaki M,et al.：“非星形细胞脑肿瘤中罕见的 p53 基因突变 - 通过酵母功能测定进行重新评估。”

Tada M: p53 mutation and its functional influences.Saya H (eds) "p53-Molecular Mechanisms and Clinical Applications, Shujunsha, Tokyo, 140 (1998)

Tada M：p53 突变及其功能影响。Saya H（编辑）“p53-分子机制和临床应用”，Shujunsha，东京，140（1998）

Tada M,: "Clonality and stability of the p53 gene in human astrocytic tumor cells." International Journal of Cancer. 67. 447-450 (1996)

Tada M，：“人星形胶质细胞肿瘤细胞中 p53 基因的克隆性和稳定性。”