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Endocrine Abstracts (2022) 84 OP07-35 | DOI: 10.1530/endoabs.84.OP-07-35

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1Institute of Endocrinology, Department of Molecular Endocrinology, Institute of Endocrinology, 11694 Prague, Czech Republic, Department of Molecular Endocrinology, Prague, Czech Republic; 2Institute of Endocrinology, Department of Molecular Endocrinology, Prague, Czech Republic; 3Institute of Endocrinology, Epartment of Molecular Endocrinology, Institute of Endocrinology, 11694 Prague, Czech Republic, Department of Molecular Endocrinology, Prague, Czech Republic; 42nd Faculty of Medicine, Charles University, Department of Nuclear Medicine and Endocrinology, Department of Nuclear Medicine and Endocrinology, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Department of Nuclear Medicine and Endocrinology, Prague 1, Czech Republic; 5Dept. of Etn, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Department of Ear, Nose and Throat, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Department of Ear, Nose and Throat, Prague, Czech Republic; 6Department of Otorhinolaryngology and Head and Neck Surgery, 1st Faculty of Medicine in Charles University and University Hospital Motol, Prague, Czech Republic, Motol University Hospital, Department of Otorhinolaryngology and Head and Neck Surgery, Prague, Czech Republic; 7Department of Surgery, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Motol University Hospital, Department of Surgery, Prague, Czech Republic; 8Department of Pathology and Molecular Medicine, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Motol University Hospital, Department of Pathology and Molecular Medicine, Prague 5, Czech Republic; 9Department of Otorhinolaryngology and Head and Neck Surgery, 3rd Faculty of Medicine, Charles University in Prague, Royal Vinohrady Teaching Hospital, University Hospital Kralovske Vinohrady, Department of Otorhinolaryngology, Prague, Czech Republic; 10Department of Pathology, 3rd Faculty of Medicine, Charles University in Prague, Royal Vinohrady Teaching Hospital, University Hospital Kralovske Vinohrady, Department of Pathology, Prague, Czech Republic; 11Military University Hospital, Military University Hospital, Department of Otorhinolaryngology and Maxillofacial Surgery, Prague, Czech Republic; 12Military University Hospital, Military University Hospital, Department of Pathology, Prague, Czech Republic


Objectives: RET fusion genes are known driver mutations in papillary thyroid carcinomas (PTCs) and have been described mainly in pediatric PTCs, in which they represent the most common genetic alteration. The aims of this study were to identify RET fusion genes in PTCs (from pediatric as well as adult patients), to correlate them with clinical and histopathological features and to determine the prognostic significance of RET fusion genes based on long-term follow-up of patients with PTC harboring this mutation.

Methods: The cohort consisted of 920 PTC samples (fresh frozen tissues) from pediatric and adult patients. Based on the detected mutation, samples were triaged. Samples positive for the BRAF, HRAS, KRAS, NRAS or NTRK fusion gene mutations were excluded from the further RET fusion gene analyses. Samples were analyzed for the presence of RET fusion genes using Real-Time PCR (LC480, Roche) or using the FusionPlex Comprehensive Thyroid and Lung panel (ArcherDx) by next generation sequencing (MiSeq, Illumina).

Results: RET fusion genes were detected in 108 (11.7%) PTCs, from which 34/121 (28.1%) were from pediatric and adolescent patients (7-20 years old) and 74/799 (9.3%) were from adult patients. The mean age of diagnosis was 33.0 ± 17.1 years. A total of 20 types of RET fusions were found, including the following partner genes: CCDC6, NCOA4, PRKAR1A, SQSTM1, IKBKG, RASAL2, TPR, ACBD5, RUFY2, BBIP1, AFAP1L2, AKAP13, TRIM27, SPECC1L, FBXO41, GOLGA5, SSBP2, ZMYM2, ERC1, KIAA1217. The RET fusion-positive carcinomas were associated with infiltrative tumor growth, numerous intrathyroidal micrometastases, psammoma bodies, lymph node and distant metastases. Lymph node metastases were found in 31/34 (91.2%) pediatric cases and in 52/71 (73.2%) adult patients. Distant metastases were identified in 9/34 (26.5%) pediatric patients and 11/69 (15.9%) adult patients. Patients responded well to radioiodine treatment, radioiodine-refractory PTCs harboring RET fusions were rare. Three patients (2.8%) died of the disease, in two cases was carcinoma positive for NCOA4/RET and in one case for CCDC6/RET with a TERT C250T co-alteration.

Conclusion: In summary, RET fusion genes are an important genetic marker in PTCs associated with aggressive tumor behavior and frequent metastases. RET fusions occurred approximately three times more frequently in pediatric and adolescent patients, in which carcinomas were more advanced, than in adult patients. In conclusion, the genetic molecular testing of RET fusions is important for patient’s diagnosis and prognosis and also for possible targeted therapy.

Supported by AZV NU21-01-00448 and MH CR RVO 00023761.

Volume 84

44th Annual Meeting of the European Thyroid Association (ETA) 2022

Brussels, Belgium
10 Sep 2022 - 13 Sep 2022

European Thyroid Association 

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