Driver Roles of a Novel Fusion Gene Discovered in Thyroid Carcinomas

Abstract

Introduction: Thyroid cancer incidence is increasing. Follicular variant papillary thyroid carcinomas (fvPTC) are hard to diagnose and genetic alterations are largely unknown. Discovery of novel alteration(s) might aid diagnosis of fvPTCs. Methods: RNA sequencing was performed on 70 cases of thyroid carcinoma tissues including 9 fvPTCs. Findings of fusion transcripts were validated by RT-PCR in additional 20 cases of fvPTC samples. Structural analysis was performed to determine the fusion transcripts driver role in oncogenesis. A cell line model has been generated and its transforming phenotype was examined in soft agar assays. Phospho-kinase assay was performed to reveal the underlying molecular mechanisms. Results: A novel EZR-ERBB4 fusion has been discovered. It was mutually exclusive with previously known thyroid oncogenes, and structurally a driver function has been expected. In a cell line model the fusion gene showed oncogenic phenotype. Phosphorylation of STAT3 was associated with the transformation. Conclusion: Based on the results a driver role of EZR-ERBB4 might be considered in fvPTCs.