Development and Application of Yeast Stop Codon Assay for Tumor Suppressor Genes in Brain Tumors

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In this project, we aimed to identify genes mutated in human brain tumors, by establishing yeast-based assays for chain-terminating mutations, as a new molecular diagnostic tool. We have successfully obtained the following results.1) We have demonstrated combined mutation or deletion of p53, PTEN, p16, p14ARF genes in human glioblastoma cells (Brain Pathol, 1999).2) We have demonstrated the role of p53 mutation in malignant progression from low grade astrocytoma to glioblastoma (Oncogene, 1999, Cancer Res, 1999)3) We have established a yeast assay for p73, and applied it to human brain tumors, together with analyzing the function of the p73 C-terminal part (Cancer Res, 1999 ; Brain Pathol, 2001).4) We established a PTEN stop codon assay, and demonstrated mutation of PTEN and expression of ψPTEN in glioblastomas (Oncogene, 2000).5) We established an APC stop codon assay, and applied it to brain tumors, colon cancers, and breast cancers (Am J Pathol, 2000)6) We have established an NF2 stop codon assay and a "Universal stop codon assay", and applied them to various human tumors (manuscripts in preparation).