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 <i>RET</i> proto-oncogene underlie the development of hereditary medullary thyroid carcinoma (MTC). The aims of this study were to evaluate the prevalence of germline <i>RET</i> mutations in a large series of MTC, collec...
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| Format: | Article |
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MDPI AG
2019-09-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/10/9/698 |
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doaj-c40740a3072644b890ca3b1a1079e1bb2020-11-25T01:31:51ZengMDPI AGGenes2073-44252019-09-0110969810.3390/genes10090698genes10090698Twenty-Five Years Experience on RET Genetic Screening on Hereditary MTC: An Update on The Prevalence of Germline RET MutationsRossella Elisei0Alessia Tacito1Teresa Ramone2Raffaele Ciampi3Valeria Bottici4Virginia Cappagli5David Viola6Antonio Matrone7Loredana Lorusso8Laura Valerio9Carlotta Giani10Cristina Campopiano11Alessandro Prete12Laura Agate13Eleonora Molinaro14Cristina Romei15Department of Clinical and Experimental Medicine, Unit of Endocrinology University of Pisa, 56124 Pisa, ItalyDepartment of Clinical and Experimental Medicine, Unit of Endocrinology University of Pisa, 56124 Pisa, ItalyDepartment of Clinical and Experimental Medicine, Unit of Endocrinology University of Pisa, 56124 Pisa, ItalyDepartment of Clinical and Experimental Medicine, Unit of Endocrinology University of Pisa, 56124 Pisa, ItalyDepartment of Clinical and Experimental Medicine, Unit of Endocrinology University of Pisa, 56124 Pisa, ItalyDepartment of Clinical and Experimental Medicine, Unit of Endocrinology University of Pisa, 56124 Pisa, ItalyDepartment of Clinical and Experimental Medicine, Unit of Endocrinology University of Pisa, 56124 Pisa, ItalyDepartment of Clinical and Experimental Medicine, Unit of Endocrinology University of Pisa, 56124 Pisa, ItalyDepartment of Clinical and Experimental Medicine, Unit of Endocrinology University of Pisa, 56124 Pisa, ItalyDepartment of Clinical and Experimental Medicine, Unit of Endocrinology University of Pisa, 56124 Pisa, ItalyDepartment of Clinical and Experimental Medicine, Unit of Endocrinology University of Pisa, 56124 Pisa, ItalyDepartment of Clinical and Experimental Medicine, Unit of Endocrinology University of Pisa, 56124 Pisa, ItalyDepartment of Clinical and Experimental Medicine, Unit of Endocrinology University of Pisa, 56124 Pisa, ItalyDepartment of Clinical and Experimental Medicine, Unit of Endocrinology University of Pisa, 56124 Pisa, ItalyDepartment of Clinical and Experimental Medicine, Unit of Endocrinology University of Pisa, 56124 Pisa, ItalyDepartment of Clinical and Experimental Medicine, Unit of Endocrinology University of Pisa, 56124 Pisa, ItalyBackground: Pathogenic germline mutations affecting the <i>RET</i> proto-oncogene underlie the development of hereditary medullary thyroid carcinoma (MTC). The aims of this study were to evaluate the prevalence of germline <i>RET</i> mutations in a large series of MTC, collected over the last 25 years, and to reappraise their clinical significance. Methods: We performed <i>RET</i> genetic screening in 2031 Italian subjects: patients who presented with sporadic (n = 1264) or hereditary (n = 117) MTC, plus 650 relatives. Results: A <i>RET</i> 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) <i>RET</i> 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 <i>RET</i> screening, some VUS can be found but their pathogenic role must be demonstrated before screening the family.https://www.mdpi.com/2073-4425/10/9/698medullary thyroid carcinomagenetic screening<i>RET</i>VUS |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Rossella Elisei Alessia Tacito Teresa Ramone Raffaele Ciampi Valeria Bottici Virginia Cappagli David Viola Antonio Matrone Loredana Lorusso Laura Valerio Carlotta Giani Cristina Campopiano Alessandro Prete Laura Agate Eleonora Molinaro Cristina Romei |
| spellingShingle |
Rossella Elisei Alessia Tacito Teresa Ramone Raffaele Ciampi Valeria Bottici Virginia Cappagli David Viola Antonio Matrone Loredana Lorusso Laura Valerio Carlotta Giani Cristina Campopiano Alessandro Prete Laura Agate Eleonora Molinaro Cristina Romei Twenty-Five Years Experience on RET Genetic Screening on Hereditary MTC: An Update on The Prevalence of Germline RET Mutations Genes medullary thyroid carcinoma genetic screening <i>RET</i> VUS |
| author_facet |
Rossella Elisei Alessia Tacito Teresa Ramone Raffaele Ciampi Valeria Bottici Virginia Cappagli David Viola Antonio Matrone Loredana Lorusso Laura Valerio Carlotta Giani Cristina Campopiano Alessandro Prete Laura Agate Eleonora Molinaro Cristina Romei |
| author_sort |
Rossella Elisei |
| title |
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_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_sort |
twenty-five years experience on ret genetic screening on hereditary mtc: an update on the prevalence of germline ret mutations |
| publisher |
MDPI AG |
| series |
Genes |
| issn |
2073-4425 |
| publishDate |
2019-09-01 |
| description |
Background: Pathogenic germline mutations affecting the <i>RET</i> proto-oncogene underlie the development of hereditary medullary thyroid carcinoma (MTC). The aims of this study were to evaluate the prevalence of germline <i>RET</i> mutations in a large series of MTC, collected over the last 25 years, and to reappraise their clinical significance. Methods: We performed <i>RET</i> genetic screening in 2031 Italian subjects: patients who presented with sporadic (n = 1264) or hereditary (n = 117) MTC, plus 650 relatives. Results: A <i>RET</i> 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) <i>RET</i> 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 <i>RET</i> screening, some VUS can be found but their pathogenic role must be demonstrated before screening the family. |
| topic |
medullary thyroid carcinoma genetic screening <i>RET</i> VUS |
| url |
https://www.mdpi.com/2073-4425/10/9/698 |
| work_keys_str_mv |
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1725084873029320704 |