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- Title
Targetable gene fusions identified in radioactive iodine refractory advanced thyroid carcinoma.
- Authors
van der Tuin, K.; Garcia, M. Ventayol; Corver, W. E.; Khalifa, M. N.; RuanoNeto, D.; Corssmit, E. P. M.; Hes, F. J.; Links, T. P.; Smit, J. W. A.; Plantinga, T. S.; Kapiteijn, E.; van Wezel, T.; Morreau, H.
- Abstract
Objective: Gene alterations leading to activation of the MAPK pathway are of interest for targeted therapy in patients with advanced radioactive iodine refractory (RAI-R) thyroid carcinoma. Due to technical reasons gene fusion analysis in RNA isolated from formalin-fixed tumor tissues has till now b een limited. The objective of the present study was to identify targetable gene rearrangements in RNA isolated from fo rmalin-fixed RAI-R thyroid carcinomas. Design: Retrospective study in 132 patients with RAI-R thyroid carcinoma (59 papillary-, 24 follicular-, 35 Hürthle cell- and 14 anaplastic thyroid carcinoma). Methods: Total nucleic acid (undivided DNA and RNA) was isolated from f ormalin-fixed tissue. Extensive gene fusion analysis was performed in all samples that tested negative for pathogenic BRAF, NRAS, HRAS and KRAS variants. Results: Seven targetable gene fusions were identified in the remaining 60 samples without known DNA variants. This includes frequently reported gene fusions such as CCDC6/RET (PTC1), PRKAR1A/RET (PTC2) and ETV6/NTRK3 , and gene fusions that are less common in thyroid cancer (TPM3/NTRK1, EML4/ALK and EML4/NTRK3). Of note, most gene fusions were detected in papillary thyroid carcinoma and MAPK-associated alterations in Hürthle cell carcinomas are rare (2/35). Conclusion: Targetable gene fusions were found in 12% of RAI-R thyroid car cinoma without DNA variants and can be effectively identified in formalin-fixed tissue. These gene fus ions might provide a preclinical rationale to include specific kinase inhibitors in the treatment regimen for these pa tients. The latter intends to restore iodine transport and/or take advantage of the direct effect on tumor cell vitalit y once progressive disease is seen.
- Subjects
RAS oncogenes; GENE fusion; IODINE isotopes; ANAPLASTIC thyroid cancer; THYROID cancer; MEDULLARY thyroid carcinoma; GENE rearrangement; RNA analysis
- Publication
European Journal of Endocrinology, 2019, Vol 180, Issue 4, p235
- ISSN
0804-4643
- Publication type
Article
- DOI
10.1530/EJE-18-0653