Next Article in Journal
Reconstruction and Analysis of Gene Networks of Human Neurotransmitter Systems Reveal Genes with Contentious Manifestation for Anxiety, Depression, and Intellectual Disabilities
Next Article in Special Issue
Molecular Alterations in Thyroid Cancer: From Bench to Clinical Practice
Previous Article in Journal
BRCA2 Deletion Induces Alternative Lengthening of Telomeres in Telomerase Positive Colon Cancer Cells
Previous Article in Special Issue
Thyroid Cancer: The Quest for Genetic Susceptibility Involving DNA Repair Genes
Open AccessArticle

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

Department of Clinical and Experimental Medicine, Unit of Endocrinology University of Pisa, 56124 Pisa, Italy
Author to whom correspondence should be addressed.
Genes 2019, 10(9), 698;
Received: 8 July 2019 / Accepted: 9 August 2019 / Published: 10 September 2019
(This article belongs to the Special Issue Thyroid Cancer: Genetics and Targeted Therapies)
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. View Full-Text
Keywords: medullary thyroid carcinoma; genetic screening; RET; VUS medullary thyroid carcinoma; genetic screening; RET; VUS
Show Figures

Figure 1

MDPI and ACS Style

Elisei, R.; Tacito, A.; Ramone, T.; Ciampi, R.; Bottici, V.; Cappagli, V.; Viola, D.; Matrone, A.; Lorusso, L.; Valerio, L.; Giani, C.; Campopiano, C.; Prete, A.; Agate, L.; Molinaro, E.; Romei, C. Twenty-Five Years Experience on RET Genetic Screening on Hereditary MTC: An Update on The Prevalence of Germline RET Mutations. Genes 2019, 10, 698.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map

Back to TopTop