Abstract 5311: The tumorigenic fusion FGFR3-TACC3 escapes miR-99a regulation in glioblastoma .

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Fusion genes are common chromosomal aberrations in many cancers, and can be used as prognostic markers and drug targets in clinical practice. We used whole transcriptome sequencing to search for fusion genes in glioma and discovered FGFR3-TACC3 fusions in 4 / 48 glioblastoma but not in any of 43 low- grade glioma samples. The fusion, caused by tandem duplication on 4p16.3, was found in patients of both Caucasian and Asian origin, and was mutually exclusive with EGFR/PDGFR/MET amplification. The 3’-untranslated region (3’-UTR) of FGFR3 is lost in the fusion, and we show that this leads to elevated fusion gene expression through loss of miR-99a regulation. The fusion protein promoted cell proliferation in vitro and tumor progression in vivo, while WT FGFR3 was not tumorigenic even under forced overexpression. Citation Format: Wei Zhang, Brittany C. Parker, Matti J. Annala, David Cogdell, Kirsi Granberg, Yan Sun, Ping Ji, Xia Li, Joy Gumin, Hong Zheng, Limei Hu, Raymond Sawaya, Gregory Fuller, Kexin Chen, Frederick L. Lang, Matti Nykter. The tumorigenic fusion FGFR3-TACC3 escapes miR-99a regulation in glioblastoma . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5311. doi:10.1158/1538-7445.AM2013-5311