FGFR3-TACCs3 Fusions and Their Clinical Relevance in Human Glioblastoma

Abstract

Oncogenic fusion genes have emerged as successful targets in several malignancies, such as chronic myeloid leukemia and lung cancer. Fusion of the fibroblast growth receptor 3 and the transforming acidic coiled coil containing protein-FGFR3-TACC3 fusion-is prevalent in 3-4% of human glioblastoma. The fusion protein leads to the constitutively activated kinase signaling of FGFR3 and thereby promotes cell proliferation and tumor progression. The subgroup of FGFR3-TACC3 fusion-positive glioblastomas presents with recurrent clinical and histomolecular characteristics, defining a distinctive subtype of IDH-wildtype glioblastoma. This review aims to provide an overview of the available literature on FGFR3-TACC3 fusions in glioblastoma and possible implications for actual clinical practice.

Keywords: FGFR; FGFR3-TACC3; TACC; glioblastoma; molecular diagnostics; molecular signaling; oncogenic fusion; tyrosine kinase receptors.

Figure 1

FGFR kinase signaling and activation of MAPK pathways leading to cell proliferation and cell survival (created with biorender.com, accessed on 21 May 2022).

Figure 2

The FGFR3 and the TACC3 gene are both located on chromosome 4p16.3. The oncogenic fusion gene codes for FGFR3, harboring an intact kinase domain fused to the TACC3 gene, including the functioning coiled-coil domain (created with biorender.com, accessed on 21 May 2022).