ETA2023 45th Annual Meeting of the European Thyroid Association ETA 2023 Oral Session 12: Emerging Insights into Thyroid Cancer Genetics (5 abstracts)
Braf fusion genes in a large cohort of thyroid carcinomas
Barbora Bulanova 1 , Vlasta Sykorova 2 , Karolina Mastnikova 2 , Eliska Vaclavikova 2 , Jitka Moravcova 2 , Petr Vlcek 3 , Petr Lastuvka 4 , Rami Katra 5 , Petr Bavor 6 , Daniela Novakova Kodetova 7 , Martin Chovanec 8 , Jana Drozenova 9 , Jaromir Astl 10 , Petr Hrabal 11 , Josef Vcelak 2 & Bela Bendlova 2
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; 3Motol University Hospital, Department of Nuclear Medicine and Endocrinology; 4Motol University Hospital, Department of Otorhinolaryngology and Head and Neck Surgery; 5Motol University Hospital, Department of Ear, Nose and Throat; 6Motol University Hospital, Department of Surgery; 7Motol University Hospital, Department of Pathology and Molecular Medicine; 8University Hospital Kralovske Vinohrady, Department of Otorhinolaryngology; 9University Hospital Kralovske Vinohrady, Department of Pathology; 10Military University Hospital, Department of Otorhinolaryngology and Maxillofacial Surgery; 11Military University Hospital, Department of Pathology
Objectives: Effective patient management is about finding a balance between overtreatment and undertreatment. Finding the border is very difficult due to the hardly predictable development of carcinoma. Molecular markers and their testing could help distinguish between low-grade and high- grade carcinomas. One of these molecular markers is a BRAF fusion gene. The aim of this study was to identify BRAF fusion genes in thyroid carcinomas, to correlate them with clinical and histopathological features and to determine the prognostic significance of BRAF fusion genes based on long-term follow-up of patients with carcinoma harboring this mutation.
Methods: The cohort consisted of 1161 fresh frozen thyroid carcinomas including 993 papillary thyroid carcinomas (PTCs). Based on the detected mutation, samples were triaged. Samples positive for the BRAF, HRAS, KRAS, NRAS, RET or NTRK fusion gene mutations were excluded from further BRAF fusion gene analyses. Samples were analyzed for the presence of BRAF fusion genes using the FusionPlex Comprehensive Thyroid and Lung panel (Invitae) by next-generation sequencing (MiSeq, Illumina).
Results: BRAF fusion genes were detected in 33/993 (3.3%) PTCs, of which 3/124 (2.4%) were from pediatric and adolescent patients (2-20 years old) and 30/869 (3.5%) from adult patients with PTC. The mean age of diagnosis was 46.2 ± 17.8 years and the female to male ratio was 3.7:1. A total of 23 types of BRAF fusions were found, including the following partner genes: ABCC1, AGK, AVEN, BRWD1, C16orf74, CCNY, CHCHD3, CLIP2, CTNNAL1, CUL1, DLG1, GNAI3, MKRN1, NPAT, OPTN, PARP12, RNF150, RRM1, SLC9A8, SND1, SNX1, TNS1, TPD52. In four cases, PTC harbored not only the BRAF fusion but also the TERT mutation. Lymph node metastases were found in 11 (33.3%) patients. Distant metastases were identified in 4 (12.1%) patients. Four adult patients (12.1%) died of the disease, in three cases carcinomas were also positive for the TERT mutation.
Conclusion: In summary, there are many types of BRAF fusion genes, only a few of which were recurrent. BRAF fusions occurred with similar frequency in pediatric and adult patients, and were even slightly more frequent in adult patients. Coexistence of the TERT mutation was associated with a worse prognosis. Genetic molecular testing of BRAF fusions is important for patient’s diagnosis and prognosis and also for possible targeted therapy.
Supported by AZV NU21-01-00448 and MH CZ RVO 00023761.
Volume 92
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Endocrine Abstracts
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