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Targetable Gene Fusions Identified in Radioactive Iodine-Refractory Advanced Thyroid Carcinoma. / van der Tuin, Karin; Ventayol, Marina; Corver, Willem; Khalifa, Midia; Ruano, Dina; Corssmit, E P; Hes, Frederik J; Links, Thera P; Smit, Jan; Plantinga, Theo S; Kapiteijn, E; Van Wezel, Ton; Morreau, Hans.

In: European Journal of Endocrinology, Vol. 180, No. 4, 01.04.2019, p. 235-241.

Research output: Contribution to journalArticleResearchpeer-review

Harvard

van der Tuin, K, Ventayol, M, Corver, W, Khalifa, M, Ruano, D, Corssmit, EP, Hes, FJ, Links, TP, Smit, J, Plantinga, TS, Kapiteijn, E, Van Wezel, T & Morreau, H 2019, 'Targetable Gene Fusions Identified in Radioactive Iodine-Refractory Advanced Thyroid Carcinoma' European Journal of Endocrinology, vol. 180, no. 4, pp. 235-241. https://doi.org/10.1530/EJE-18-0653

APA

van der Tuin, K., Ventayol, M., Corver, W., Khalifa, M., Ruano, D., Corssmit, E. P., ... Morreau, H. (2019). Targetable Gene Fusions Identified in Radioactive Iodine-Refractory Advanced Thyroid Carcinoma. European Journal of Endocrinology, 180(4), 235-241. https://doi.org/10.1530/EJE-18-0653

Vancouver

van der Tuin K, Ventayol M, Corver W, Khalifa M, Ruano D, Corssmit EP et al. Targetable Gene Fusions Identified in Radioactive Iodine-Refractory Advanced Thyroid Carcinoma. European Journal of Endocrinology. 2019 Apr 1;180(4):235-241. https://doi.org/10.1530/EJE-18-0653

Author

van der Tuin, Karin ; Ventayol, Marina ; Corver, Willem ; Khalifa, Midia ; Ruano, Dina ; Corssmit, E P ; Hes, Frederik J ; Links, Thera P ; Smit, Jan ; Plantinga, Theo S ; Kapiteijn, E ; Van Wezel, Ton ; Morreau, Hans. / Targetable Gene Fusions Identified in Radioactive Iodine-Refractory Advanced Thyroid Carcinoma. In: European Journal of Endocrinology. 2019 ; Vol. 180, No. 4. pp. 235-241.

BibTeX

@article{cab1b14040b644ce8fed2ab0b6d0bd5b,
title = "Targetable Gene Fusions Identified in Radioactive Iodine-Refractory Advanced Thyroid Carcinoma",
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 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 H{\"u}rthle 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 (n=2), 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 H{\"u}rthle cell carcinomas are rare (2/35).CONCLUSION: Targetable gene fusions were found in 12{\%} of RAI-R thyroid carcinoma without DNA variants, and can be effectively identified in formalin-fixed tissue. These gene fusionsmight 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.",
keywords = "Advanced Thyroid Carcinoma, targeted therapy, advanced radioactive iodine-refractory (RAI-R) thyroid carcinoma, tumor",
author = "{van der Tuin}, Karin and Marina Ventayol and Willem Corver and Midia Khalifa and Dina Ruano and Corssmit, {E P} and Hes, {Frederik J} and Links, {Thera P} and Jan Smit and Plantinga, {Theo S} and E Kapiteijn and {Van Wezel}, Ton and Hans Morreau",
year = "2019",
month = "4",
day = "1",
doi = "10.1530/EJE-18-0653",
language = "English",
volume = "180",
pages = "235--241",
journal = "European Journal of Endocrinology",
issn = "0804-4643",
publisher = "BioScientifica Ltd.",
number = "4",

}

RIS

TY - JOUR

T1 - Targetable Gene Fusions Identified in Radioactive Iodine-Refractory Advanced Thyroid Carcinoma

AU - van der Tuin, Karin

AU - Ventayol, Marina

AU - Corver, Willem

AU - Khalifa, Midia

AU - Ruano, Dina

AU - Corssmit, E P

AU - Hes, Frederik J

AU - Links, Thera P

AU - Smit, Jan

AU - Plantinga, Theo S

AU - Kapiteijn, E

AU - Van Wezel, Ton

AU - Morreau, Hans

PY - 2019/4/1

Y1 - 2019/4/1

N2 - 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 Hürthle 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 (n=2), 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 carcinoma without DNA variants, and can be effectively identified in formalin-fixed tissue. These gene fusionsmight 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.

AB - 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 Hürthle 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 (n=2), 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 carcinoma without DNA variants, and can be effectively identified in formalin-fixed tissue. These gene fusionsmight 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.

KW - Advanced Thyroid Carcinoma

KW - targeted therapy

KW - advanced radioactive iodine-refractory (RAI-R) thyroid carcinoma

KW - tumor

UR - http://www.scopus.com/inward/record.url?scp=85062827790&partnerID=8YFLogxK

U2 - 10.1530/EJE-18-0653

DO - 10.1530/EJE-18-0653

M3 - Article

VL - 180

SP - 235

EP - 241

JO - European Journal of Endocrinology

JF - European Journal of Endocrinology

SN - 0804-4643

IS - 4

ER -

ID: 44276493