The role of TP53 gain-of-function mutation in multifocal glioblastoma
Lauren R. Olafson, Manuri Gunawardena, Sheri Nixdorf, Kerrie L. McDonald, Robert W. Rapkins
Abstract
PURPOSE: The phenotypic and genotypic landscapes in multifocal glioblastoma (MF GBM) cases can vary greatly among lesions. In a MF GBM patient, the rapid development of a secondary lesion was investigated to determine if a unique genetic signature could account for the apparent increased malignancy of this lesion. METHODS: The primary (G52) and secondary (G53) tumours were resected to develop patient derived models followed by functional assays and multiplatform molecular profiling. RESULTS: Molecular profiling revealed G52 was wild-type for TP53 while G53 presented with a TP53 missense mutation. Functional studies demonstrated increased proliferation, migration, invasion and colony formation in G53. CONCLUSION: This data suggests that the TP53 mutation led to gain-of-function phenotypes and resulted in greater overall oncogenic potential of G53.