Mdb-31. preliminary study on biological significance of wtx g435d mutation in medulloblastoma

Abstract BACKGROUND: Previously, we reported a case of familial medulloblastoma without hereditary tumor syndrome. Through analysis of the whole genome sequencing of the family members, we found a common germline WTX (c.1863C>T, p.Gly435Asp) mutation in this family: cytosine (C) at position 63411863 on X chromosome was replaced by thymine (T), and the corresponding amino acid was glycine Gly (G) at position 435, which was converted to aspartic acid Asp (D). We conduct this study to explore the biological significance of this mutation in medulloblastoma cell lines. METHODS: Medulloblastoma cells (cell lines and primary cells) with stable WTX (c.1863C > T) hybrid mutation were contstrcuted by lentivirus transfection. The effects of WTXG435D on proliferation, invasion and chemosensitivity of medulloblastoma cells were investigated in vitro and in vivo. RESULTS: Proliferation and invasion ability of WTXG435D medulloblastoma cell were significantly weaker than WTX WT cells, and they were more sensitive to radiation and chemotherapy(cisplatin, vincristine) treatment in vitro. In vivo, animal experiments also showed that intracranial in situ tumors formed by WTXG435D medulloblastoma cells were more sensitive to radiotherapy and chemotherapy than in situ tumors formed by WTXWT ones, and the survival was longer. CONCLUSION: WTX (c.1863C>T, p. Gly435Asp) mutation could reduce the proliferation and invasion ability of medulloblastoma cells, and enhance the sensitivity of radiotherapy and chemotherapy. Which could be a potential therapeutic target for further investigation.