PhD Scientific Days 2024

Budapest, 9-10 July 2024

Poster Session Q - Pathological and Oncological Sciences 2.

Comprehensive genomic profiling of pediatric papillary thyroid carcinomas reveals potential novel therapeutic approaches


Gábor Bedics1
1: Semmelweis Egyetem ÁOK Patológiai és Kísérleti Rákkutató Intézet

Text of the abstract

Tumors of the thyroid account for 0.7% of pediatric malignant diseases. Incidence of these tumors has elevated significantly over the recent decades, although the explanation for this trend is unclear yet. Routine treatment of the disease includes thyroidectomy and radioactive iodine treatment, which could significantly influence the patient’s quality of life, by causing endocrine dysfunctions and most importantly, elevating risk of developing secondary malignancies.

We aimed to perform comprehensive genomic profiling on a cohort of pediatric patients diagnosed with papillary thyroid carcinoma, to detect genomic variants serving as potential therapeutic targets, for the first time in Hungary.

Materials and methods
Comprehensive genomic profiling of histological specimens of 18 patients was performed by Illumina TruSight Oncology 500 assay, bioinformatic analysis was carried out applying Illumina TruSight Oncology 500 Local App v2.1, while clinical interpretation was accomplished by QIAGEN Clinical Insight.

Driver gene fusions were detected in 12 patients out of 18 (66.7%), with the gene fusions of the RET proto-oncogene being the most frequent partner gene (7/18, 38.9%). Five samples expressed CCDC6::RET, two samples NCOA4::RET gene fusion. NTRK1 and ALK driver rearrangements were detected in 2-2 samples, while BRAF gene fusion was revealed in 1 sample. Pathogenic mutations were detected in 6 patients: BRAFV600E, TET2P398fs*45, NTRK1Q308fs*160, EGFRR776C and CBLY371H variants. These genomic profiles raise the opportunity of molecularly targeted therapeutic approaches in 88.9% of patients in our cohort.

Our study revealed actionable genomic variants in nearly 90% of the pediatric patients diagnosed with papillary thyroid carcinoma. Application of molecularly targeted therapeutic approaches may be an attractive treatment modality among pediatric patients diagnosed with this malignancy, since (i) using these targeted therapeutic approaches may enable us to avoid potential toxicity and secondary malignancies caused by radioactive iodine therapy and (ii) may offer a novel therapeutic strategy to treat relapsed tumors and treatment-refractory cases.

This work was funded by the ÚNKP-23-4-I New National Excellence Program of the Ministry for Culture and Innovation from the National Research Development and Innovation Fund.