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Driver Roles of a Novel Fusion Gene Discovered in Thyroid Carcinomas

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Authors
지현근
Advisor
한원식
Major
의과대학 협동과정 종양생물학전공
Issue Date
2014-02
Publisher
서울대학교 대학원
Keywords
Fusion geneThyroid cancerFollicular variant papillary thyroid carcinomasDriver alterationDiagnosis
Description
학위논문 (박사)-- 서울대학교 대학원 : 협동과정 종양생물학전공, 2014. 2. 한원식.
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.
Language
English
URI
https://hdl.handle.net/10371/121764
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College of Medicine/School of Medicine (의과대학/대학원)Program in Cancer Biology (협동과정-종양생물학전공)Theses (Ph.D. / Sc.D._협동과정-종양생물학전공)
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