PhD Scientific Days 2025

Molecular Medicine V.

Genetic Background of Papillary Thyroid Carcinoma

Name of the presenter

Richard Armos

Institute/workplace of the presenter

Department of Internal Medicine and Oncology, Semmelweis University

Authors

Richard Armos¹, Bence Bojtor¹, Márton Papp², Ildikó Illyés³, Balázs Lengyel¹, András Kiss^1,3, Balázs Szili¹, Bálint Tóbiás⁴, Bernadett Balla⁴, Henriett Pikó¹, Anett Illés¹, Zsuzsanna Putz¹, Erika Tóth⁵, Andrea Kohánka⁵, János Podani⁶, István Takács¹, János Pál Kósa⁴, Péter Lakatos¹

1: Department of Internal Medicine and Oncology, Semmelweis University
2: Bioinformatics Center, University of Veterinary Medicine
3: Institute of Pathology, Forensic and Insurance Medicine, Semmelweis University
4: SE HUN-REN-TKI ENDOMOLPAT Research Group
5: Department of Surgical and Molecular Pathology, National Institute of Oncology
6: Department of Plant Systematics, Ecology and Theoretical Biology, Eötvös Loránd University

Text of the abstract

Introduction
Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy, with rising incidence worldwide and clinically heterogeneous behavior, partly driven by genetic alterations. Fusion mutations and microRNA (miRNA) expression profiles have recently emerged as promising diagnostic and therapeutic biomarkers.

Aims
This study aimed to investigate the genetic and molecular background of PTC in Hungarian cohorts.

Methods
Two independent patient populations were analyzed. In the first, next-generation sequencing was used to detect 23 types of gene fusions. In the second, we performed comprehensive miRNA profiling on PTC and normal thyroid tissues, quantifying over 2600 miRNAs. Classical and novel statistical approaches were used to analyze molecular and clinicopathological data, identify biomarkers, and explore their clinical implications.

Results
Fusion mutations were detected in 27% of PTC cases, most commonly affecting RET and NTRK3 driver genes. These alterations were more frequent in younger patients and showed associations with surgical decision-making and comorbidities. miRNA profiling revealed 30 miRNAs with significantly altered expression in tumor versus control samples. Several of these miRNAs were described in PTC for the first time by our group, while others confirmed previous findings. miRNA expression patterns reliably distinguished malignant from non-malignant tissue, suggesting potential utility in preoperative diagnostics.

Conclusion
Our findings support the value of molecular profiling in improving risk stratification and guiding therapeutic decisions in PTC. The higher prevalence of fusion mutations in younger patients highlights the potential benefit of preoperative genetic screening, especially for targetable alterations. miRNA profiling may also enhance the diagnostic accuracy of fine-needle aspiration in indeterminate cases. These results contribute to the growing role of precision oncology in PTC management.

Funding
This research was funded by the “MINISTRY OF INNOVATION AND TECHNOLOGY OF HUNGARY, grant number 2020-4.1.1.-TKP2020-MOLORKIV” and the “HUNGARIAN RESEARCH NETWORK, grant number SE HUN-REN-TKI ENDOMOLPAT”.