Molecular features of gliomas with high tumor mutational burden


Joanne Xiu, Kyle M Walsh, Manjari Pandey, Emil Lou, Ekokobe Fonkem, Herbert B. Newton, Erin M. Dunbar, Macarena Ines De La Fuente, Michael J. Glantz, Sandeep Mittal, David M. Ashley, W. Michael Korn, Ashley Love Sumrall


TMB-H is associated with POLE mutation, high rate of GC>TA transition and microsatellite instability. – GC>TA high, an indicator of alkylator-induced phenotype, is associated with MSI-H; and the concurrent GC>TA high and MSI-H further increase TMB. – MSI-H or TMB-H is not associated with increased PD-L1 expression. – Paired sample analysis confirms that temozolomide sensitivity markers including MGMT-Me and IDH mutations are more prevalent in tumors acquiring hypermutation phenotype. – Our results support the notion that unlike other cancer types, TMB-H in glioma may not associate with increased response to Immuno-Oncology therapy – Further understanding of molecular and immune profile of the TMB-H may facilitate more individualized treatment planning – A clinical trial of treating TMB-High glioma patients differentially according to the underlying molecular drivers is warranted.

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