Oncogenic transgelin-2 is differentially regulated in isocitrate dehydrogenase wild-type vs. mutant gliomas
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Sasha J. Beyer1, Erica H. Bell1, Joseph P. McElroy2, Jessica L. Fleming1, Tiantian Cui1, Aline Becker1, Emily Bassett1, Benjamin Johnson1, Pooja Gulati1, Ilinca Popp3,4, Ori Staszewski5, Marco Prinz5,6,7, Anca L. Grosu3,4, Saikh Jaharul Haque1 and Arnab Chakravarti1
1Department of Radiation Oncology, Arthur G. James Hospital/The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA
2Center for Biostatistics, The Ohio State University, Columbus, OH, USA
3Department of Radiation Oncology, Medical Center University of Freiburg, Freiburg, Germany
4German Cancer Consortium (DKTK), Partner Site, Freiburg, Germany
5Institute of Neuropathology, Medical Faculty, University of Freiburg, Freiburg, Germany
6BIOSS Centre for Biological Signaling Studies, University of Freiburg, Freiburg, Germany
7CIBSS Centre for Integrative Biological Signaling Studies, University of Freiburg, Freiburg, Germany
Arnab Chakravarti, email: firstname.lastname@example.org
Keywords: transgelin-2; glioma; glioblastoma; isocitrate dehydrogenase (IDH1/2) mutation; invasion
Received: October 06, 2018 Accepted: October 24, 2018 Published: December 14, 2018
The presence of an isocitrate dehydrogenase (IDH1/2) mutation in gliomas is associated with favorable outcomes compared to gliomas without the mutation (IDH1/2 wild-type, WT). The underlying biological mechanisms accounting for improved clinical outcomes in IDH1/2 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 IDH1/2 WT versus IDH1/2 mutant Grade II and III gliomas and identified transgelin-2 (TAGLN2), an oncogene and actin-polymerizing protein, to be expressed at significantly higher levels in IDH1/2 WT gliomas compared to IDH1/2 mutant gliomas. This differential expression of TAGLN2 was primarily due to promoter hypermethylation in IDH1/2 mutant gliomas, suggesting involvement of TAGLN2 in the G-CIMP. Our results also suggest that TAGLN2 may be involved in progression due to higher expression in glioblastomas compared to IDH1/2 WT gliomas of lower grades. Furthermore, our results suggest that TAGLN2 functions as an oncogene by contributing to proliferation and invasion when overexpressed in IDH1/2 WT glioma cells. Taken together, this study demonstrates a possible link between increased TAGLN2 expression, invasion and poor patient outcomes in IDH1/2 WT gliomas and identifies TAGLN2 as a potential novel therapeutic target for IDH1/2 WT gliomas.
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