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Article

Higher RET Gene Expression Levels Do Not Represent anAlternative RET Activation Mechanism in Medullary Thyroid Carcinoma

1
Endocrine Unit, Department of Clinical and Experimental Medicine, University of Pisa, 56124 Pisa, Italy
2
Department of Surgical, Medical, Molecular Pathology, University of Pisa, 56124 Pisa, Italy
*
Author to whom correspondence should be addressed.
Biomolecules 2021, 11(10), 1542; https://doi.org/10.3390/biom11101542
Submission received: 2 September 2021 / Revised: 7 October 2021 / Accepted: 14 October 2021 / Published: 19 October 2021

Abstract

This study was designed to investigate whether RET (rearranged during transfection) mRNA over-expression could be considered an alternative driver event for the development of medullary thyroid carcinoma (MTC), and if different RET isoforms could play a role in MTC tumorigenesis. Eighty-three MTC patients, whose mutational profile was previously identified by next-generation sequencing (NGS) IONS5, were included in this study. Expression analysis was performed by the quantitative reverse transcription-polymerase chain reaction technique. RET expression levels were found to be significantly higher in cases with RET somatic mutations than in cases that were negative for RET somatic mutations (p = 0.003) as well as in cases with a somatic mutation, either in RET or RAS than in cases negative for both these mutations (p = 0.01). All cases were positive for the RET51 isoform expression while only 72/83 (86.7%) were positive for RET9 isoform expression. A statistically significant higher expression of the RET51 isoform was found in cases positive for RET somatic mutation than in cases either positive for RAS mutation (p = 0.0006) or negative for both mutations (p = 0.001). According to our data, RET gene over-expression does not play a role in MTC tumorigenesis, neither as an entire gene or as an isoform. At variance, the RET gene, and in particular the RET51 isoform, is expressed higher in RET mutated cases. On the basis of these results we can hypothesize that the overexpression of RET, and in particular of RET51, could potentiate the transforming activity of mutated RET, making these cases more aggressive.
Keywords: RET; RAS; medullary thyroid carcinoma; mRNA expression RET; RAS; medullary thyroid carcinoma; mRNA expression

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MDPI and ACS Style

Mulè, C.; Ciampi, R.; Ramone, T.; Prete, A.; Matrone, A.; Cappagli, V.; Torregrossa, L.; Basolo, F.; Elisei, R.; Romei, C. Higher RET Gene Expression Levels Do Not Represent anAlternative RET Activation Mechanism in Medullary Thyroid Carcinoma. Biomolecules 2021, 11, 1542. https://doi.org/10.3390/biom11101542

AMA Style

Mulè C, Ciampi R, Ramone T, Prete A, Matrone A, Cappagli V, Torregrossa L, Basolo F, Elisei R, Romei C. Higher RET Gene Expression Levels Do Not Represent anAlternative RET Activation Mechanism in Medullary Thyroid Carcinoma. Biomolecules. 2021; 11(10):1542. https://doi.org/10.3390/biom11101542

Chicago/Turabian Style

Mulè, Chiara, Raffaele Ciampi, Teresa Ramone, Alessandro Prete, Antonio Matrone, Virginia Cappagli, Liborio Torregrossa, Fulvio Basolo, Rossella Elisei, and Cristina Romei. 2021. "Higher RET Gene Expression Levels Do Not Represent anAlternative RET Activation Mechanism in Medullary Thyroid Carcinoma" Biomolecules 11, no. 10: 1542. https://doi.org/10.3390/biom11101542

APA Style

Mulè, C., Ciampi, R., Ramone, T., Prete, A., Matrone, A., Cappagli, V., Torregrossa, L., Basolo, F., Elisei, R., & Romei, C. (2021). Higher RET Gene Expression Levels Do Not Represent anAlternative RET Activation Mechanism in Medullary Thyroid Carcinoma. Biomolecules, 11(10), 1542. https://doi.org/10.3390/biom11101542

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