Cellular migration in IDH-wildtype glioblastoma: a case series on the genomics of amoeboid movement and its prognostic significance

Glioblastoma is an aggressive, fatal form of adult diffuse glioma. The ability of glioblastoma cells to switch to an amoeboid-like mode of invasion contributes greatly to tumour aggressiveness,1 though the prognostic value of genes related to amoeboid migration are not well characterised. Aims: To explore genes involved in amoeboid-related events (AREs) and determine differences in the frequency of genomic alterations between different adult glioma subgroups. Methods: An extensive literature review was conducted to identify genes involved in AREs. The genomic alteration frequency of identified ARE-associated genes were compared between low and high-grade glioma cohorts (LGG and HGG, respectively), stratified by their IDH1/2 mutation status. The prognostic significance of ARE-genes was also analysed using the HGG cohort. Results: Overall, 273 genes related to AREs were identified and subtyped. ARE-associated genomic alterations were significantly more common in IDH-mutant HGG, relative to IDH-wildtype HGG (p=0.048). Survival analyses indicated that novel ARE-associated genes, PIK3R6, PLA2G2F, PLA2G4B, PLA2G4F, PNPLA3, ARPC4 and WNT8A, may have prognostic value in HGG patients. Of interest, MAP2K2, was associated with longer overall survival in HGG patients. Conclusion: ARE-associated genes show varying genomic alterations between different adult glioma subtypes and represent an exciting opportunity for further investigation. Reference 1. Koh I, Cha J, Park J, et al. The mode and dynamics of glioblastoma cell invasion into a decellularized tissue-derived extracellular matrix-based three-dimensional tumor model. Sci Rep 2018; 8: 4608.