Targetable gene fusions identified in radioactive iodine refractory advanced thyroid carcinoma

van der Tuin, K., Garcia, M. V., Corver, W. E., Khalifa, M. N., Neto, D. R., Corssmit, E. P. M., Hess, F. J., Links, T. P., Smit, J. W. A., Plantinga, T. S., Kapiteijn, E., van Wezel, T. & Morreau, H., Apr-2019, In : European Journal of Endocrinology. 180, 4, p. 235-241 7 p.

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  • Targetable gene fusions identified in radioactive iodine refractory advanced thyroid carcinoma

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  • K. van der Tuin
  • M. Ventayol Garcia
  • W. E. Corver
  • M. N. Khalifa
  • D. Ruano Neto
  • E. P. M. Corssmit
  • F. J. Hess
  • T. P. Links
  • J. W. A. Smit
  • T. S. Plantinga
  • E. Kapiteijn
  • T. van Wezel
  • H. Morreau

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 been limited. The objective of the present study was to identify targetable gene rearrangements in RNA isolated from formalin-fixed RAI-R thyroid carcinomas.

Design: Retrospective study in 132 patients with RAI-R thyroid carcinoma (59 papillary-, 24 follicular-, 35 Hurthle cell-and 14 anaplastic thyroid carcinoma).

Methods: Total nucleic acid (undivided DNA and RNA) was isolated from formalin-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 Hurthle 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 fusions might provide a preclinical rationale to include specific kinase inhibitors in the treatment regimen for these patients. The latter intends to restore iodine transport and/or take advantage of the direct effect on tumor cell vitality once progressive disease is seen.

Original languageEnglish
Pages (from-to)235-241
Number of pages7
JournalEuropean Journal of Endocrinology
Issue number4
Publication statusPublished - Apr-2019



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