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

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 pa...

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Autores principales: Mulè, Chiara, Ciampi, Raffaele, Ramone, Teresa, Prete, Alessandro, Matrone, Antonio, Cappagli, Virginia, Torregrossa, Liborio, Basolo, Fulvio, Elisei, Rossella, Romei, Cristina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8533768/
https://www.ncbi.nlm.nih.gov/pubmed/34680178
http://dx.doi.org/10.3390/biom11101542
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author Mulè, Chiara
Ciampi, Raffaele
Ramone, Teresa
Prete, Alessandro
Matrone, Antonio
Cappagli, Virginia
Torregrossa, Liborio
Basolo, Fulvio
Elisei, Rossella
Romei, Cristina
author_facet Mulè, Chiara
Ciampi, Raffaele
Ramone, Teresa
Prete, Alessandro
Matrone, Antonio
Cappagli, Virginia
Torregrossa, Liborio
Basolo, Fulvio
Elisei, Rossella
Romei, Cristina
author_sort Mulè, Chiara
collection PubMed
description 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.
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spelling pubmed-85337682021-10-23 Higher RET Gene Expression Levels Do Not Represent anAlternative RET Activation Mechanism in Medullary Thyroid Carcinoma Mulè, Chiara Ciampi, Raffaele Ramone, Teresa Prete, Alessandro Matrone, Antonio Cappagli, Virginia Torregrossa, Liborio Basolo, Fulvio Elisei, Rossella Romei, Cristina Biomolecules Article 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. MDPI 2021-10-19 /pmc/articles/PMC8533768/ /pubmed/34680178 http://dx.doi.org/10.3390/biom11101542 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mulè, Chiara
Ciampi, Raffaele
Ramone, Teresa
Prete, Alessandro
Matrone, Antonio
Cappagli, Virginia
Torregrossa, Liborio
Basolo, Fulvio
Elisei, Rossella
Romei, Cristina
Higher RET Gene Expression Levels Do Not Represent anAlternative RET Activation Mechanism in Medullary Thyroid Carcinoma
title Higher RET Gene Expression Levels Do Not Represent anAlternative RET Activation Mechanism in Medullary Thyroid Carcinoma
title_full Higher RET Gene Expression Levels Do Not Represent anAlternative RET Activation Mechanism in Medullary Thyroid Carcinoma
title_fullStr Higher RET Gene Expression Levels Do Not Represent anAlternative RET Activation Mechanism in Medullary Thyroid Carcinoma
title_full_unstemmed Higher RET Gene Expression Levels Do Not Represent anAlternative RET Activation Mechanism in Medullary Thyroid Carcinoma
title_short Higher RET Gene Expression Levels Do Not Represent anAlternative RET Activation Mechanism in Medullary Thyroid Carcinoma
title_sort higher ret gene expression levels do not represent analternative ret activation mechanism in medullary thyroid carcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8533768/
https://www.ncbi.nlm.nih.gov/pubmed/34680178
http://dx.doi.org/10.3390/biom11101542
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