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

Genes

Laura Valerio¹  Teresa Ramone¹  Virginia Cappagli¹  Eleonora Molinaro¹  Valeria Bottici¹  Antonio Matrone¹  Cristina Campopiano¹  Raffaele Ciampi¹  Alessandro Prete¹  Rossella Elisei¹  Cristina Romei¹  Alessia Tacito¹  David Viola¹  Loredana Lorusso¹  Laura Agate¹  Carlotta Giani¹ 

[1] Department of Clinical and Experimental Medicine, Unit of Endocrinology University of Pisa, 56124 Pisa, Italy;

关键词: medullary thyroid carcinoma;    genetic screening;    RET;    VUS;   

DOI  :  10.3390/genes10090698

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown