Oncogenic transgelin-2 is differentially regulated in isocitrate dehydrogenase wild-type vs. mutant gliomas

• Published in: Oncotarget 2018-12, Vol.9 (98), p.37097-37111
• Main Authors: Beyer, Sasha J, Bell, Erica H, McElroy, Joseph P, Fleming, Jessica L, Cui, Tiantian, Becker, Aline, Bassett, Emily, Johnson, Benjamin, Gulati, Pooja, Popp, Ilinca, Staszewski, Ori, Prinz, Marco, Grosu, Anca L, Haque, Saikh Jaharul, Chakravarti, Arnab
• Format: Article
• Language: English
• Subjects: Research Paper
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.26365

The presence of an ( ) mutation in gliomas is associated with favorable outcomes compared to gliomas without the mutation ( wild-type, WT). The underlying biological mechanisms accounting for improved clinical outcomes in mutant gliomas remain poorly understood, but may, in part, be due to the glioma CpG island methylator phenotype (G-CIMP) and epigenetic silencing of genes. We performed profiling of WT versus mutant Grade II and III gliomas and identified ( ), an oncogene and actin-polymerizing protein, to be expressed at significantly higher levels in WT gliomas compared to mutant gliomas. This differential expression of was primarily due to promoter hypermethylation in mutant gliomas, suggesting involvement of in the G-CIMP. Our results also suggest that may be involved in progression due to higher expression in glioblastomas compared to WT gliomas of lower grades. Furthermore, our results suggest that functions as an oncogene by contributing to proliferation and invasion when overexpressed in WT glioma cells. Taken together, this study demonstrates a possible link between increased expression, invasion and poor patient outcomes in WT gliomas and identifies as a potential novel therapeutic target for WT gliomas.