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 the whole genome sequencing family members, found 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 corresponding amino acid glycine Gly (G) 435, which converted to aspartic Asp (D). We conduct study explore biological significance cell lines. METHODS: Medulloblastoma cells (cell lines primary cells) with stable (c.1863C > T) hybrid were contstrcuted lentivirus transfection. The effects WTXG435D proliferation, invasion chemosensitivity investigated vitro vivo. RESULTS: Proliferation ability significantly weaker than WT cells, they more sensitive radiation chemotherapy(cisplatin, vincristine) treatment vitro. In vivo, animal experiments also showed that intracranial situ tumors formed radiotherapy chemotherapy WTXWT ones, survival longer. CONCLUSION: p. Gly435Asp) could reduce proliferation enhance sensitivity chemotherapy. Which be potential therapeutic target for further investigation.