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

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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.