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Twenty-Five Years Experience on RET Genetic Screening on Hereditary MTC: An Update on The Prevalence of Germline RET Mutations

Background: Pathogenic germline mutations affecting the RET proto-oncogene underlie the development of hereditary medullary thyroid carcinoma (MTC). The aims of this study were to evaluate the prevalence of germline RET mutations in a large series of MTC, collected over the last 25 years, and to rea...

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Autores principales: Elisei, Rossella, Tacito, Alessia, Ramone, Teresa, Ciampi, Raffaele, Bottici, Valeria, Cappagli, Virginia, Viola, David, Matrone, Antonio, Lorusso, Loredana, Valerio, Laura, Giani, Carlotta, Campopiano, Cristina, Prete, Alessandro, Agate, Laura, Molinaro, Eleonora, Romei, Cristina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6771015/
https://www.ncbi.nlm.nih.gov/pubmed/31510104
http://dx.doi.org/10.3390/genes10090698
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author Elisei, Rossella
Tacito, Alessia
Ramone, Teresa
Ciampi, Raffaele
Bottici, Valeria
Cappagli, Virginia
Viola, David
Matrone, Antonio
Lorusso, Loredana
Valerio, Laura
Giani, Carlotta
Campopiano, Cristina
Prete, Alessandro
Agate, Laura
Molinaro, Eleonora
Romei, Cristina
author_facet Elisei, Rossella
Tacito, Alessia
Ramone, Teresa
Ciampi, Raffaele
Bottici, Valeria
Cappagli, Virginia
Viola, David
Matrone, Antonio
Lorusso, Loredana
Valerio, Laura
Giani, Carlotta
Campopiano, Cristina
Prete, Alessandro
Agate, Laura
Molinaro, Eleonora
Romei, Cristina
author_sort Elisei, Rossella
collection PubMed
description Background: Pathogenic germline mutations affecting the RET proto-oncogene underlie the development of hereditary medullary thyroid carcinoma (MTC). The aims of this study were to evaluate the prevalence of germline RET mutations in a large series of MTC, collected over the last 25 years, and to reappraise their clinical significance. Methods: We performed RET genetic screening in 2031 Italian subjects: patients who presented with sporadic (n = 1264) or hereditary (n = 117) MTC, plus 650 relatives. Results: A RET germline mutation was found in 115/117 (98.3%) hereditary and in 78/1264 (6.2%) apparently sporadic cases: in total, 42 distinct germline variants were found. The V804M mutation was the most prevalent in our cohort, especially in cases that presented as sporadic, while mutations affecting cysteine residues were the most frequent in the group of clinically hereditary cases. All M918T mutations were “de novo” and exclusively associated with MEN2B. Several variants of unknown significance (VUS) were also found. Conclusions: a) RET genetic screening is informative in both hereditary and sporadic MTC; b) the prevalence of different mutations varies with V804M being the most frequent; c) the association genotype–phenotype is confirmed; d) by RET screening, some VUS can be found but their pathogenic role must be demonstrated before screening the family.
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spelling pubmed-67710152019-10-30 Twenty-Five Years Experience on RET Genetic Screening on Hereditary MTC: An Update on The Prevalence of Germline RET Mutations Elisei, Rossella Tacito, Alessia Ramone, Teresa Ciampi, Raffaele Bottici, Valeria Cappagli, Virginia Viola, David Matrone, Antonio Lorusso, Loredana Valerio, Laura Giani, Carlotta Campopiano, Cristina Prete, Alessandro Agate, Laura Molinaro, Eleonora Romei, Cristina Genes (Basel) Article Background: Pathogenic germline mutations affecting the RET proto-oncogene underlie the development of hereditary medullary thyroid carcinoma (MTC). The aims of this study were to evaluate the prevalence of germline RET mutations in a large series of MTC, collected over the last 25 years, and to reappraise their clinical significance. Methods: We performed RET genetic screening in 2031 Italian subjects: patients who presented with sporadic (n = 1264) or hereditary (n = 117) MTC, plus 650 relatives. Results: A RET germline mutation was found in 115/117 (98.3%) hereditary and in 78/1264 (6.2%) apparently sporadic cases: in total, 42 distinct germline variants were found. The V804M mutation was the most prevalent in our cohort, especially in cases that presented as sporadic, while mutations affecting cysteine residues were the most frequent in the group of clinically hereditary cases. All M918T mutations were “de novo” and exclusively associated with MEN2B. Several variants of unknown significance (VUS) were also found. Conclusions: a) RET genetic screening is informative in both hereditary and sporadic MTC; b) the prevalence of different mutations varies with V804M being the most frequent; c) the association genotype–phenotype is confirmed; d) by RET screening, some VUS can be found but their pathogenic role must be demonstrated before screening the family. MDPI 2019-09-10 /pmc/articles/PMC6771015/ /pubmed/31510104 http://dx.doi.org/10.3390/genes10090698 Text en © 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Elisei, Rossella
Tacito, Alessia
Ramone, Teresa
Ciampi, Raffaele
Bottici, Valeria
Cappagli, Virginia
Viola, David
Matrone, Antonio
Lorusso, Loredana
Valerio, Laura
Giani, Carlotta
Campopiano, Cristina
Prete, Alessandro
Agate, Laura
Molinaro, Eleonora
Romei, Cristina
Twenty-Five Years Experience on RET Genetic Screening on Hereditary MTC: An Update on The Prevalence of Germline RET Mutations
title Twenty-Five Years Experience on RET Genetic Screening on Hereditary MTC: An Update on The Prevalence of Germline RET Mutations
title_full Twenty-Five Years Experience on RET Genetic Screening on Hereditary MTC: An Update on The Prevalence of Germline RET Mutations
title_fullStr Twenty-Five Years Experience on RET Genetic Screening on Hereditary MTC: An Update on The Prevalence of Germline RET Mutations
title_full_unstemmed Twenty-Five Years Experience on RET Genetic Screening on Hereditary MTC: An Update on The Prevalence of Germline RET Mutations
title_short Twenty-Five Years Experience on RET Genetic Screening on Hereditary MTC: An Update on The Prevalence of Germline RET Mutations
title_sort twenty-five years experience on ret genetic screening on hereditary mtc: an update on the prevalence of germline ret mutations
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6771015/
https://www.ncbi.nlm.nih.gov/pubmed/31510104
http://dx.doi.org/10.3390/genes10090698
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