RET Proto-Oncogene in Sardinia: V804M Is the Most Frequent Mutation and May Be Associated with FMTC/MEN-2A Phenotype
- 1 February 2007
- journal article
- research article
- Published by Mary Ann Liebert Inc in Thyroid®
- Vol. 17 (2), 101-104
- https://doi.org/10.1089/thy.2006.0198
Abstract
Objective: Genetic screening of RET proto-oncogene is a powerful tool for the early identification of familial cases of medullary thyroid carcinoma (MTC), comprising isolated familial thyroid medullary carcinoma (FMTC) and multiple endocrine neoplasia syndromes 2A (MEN-2A) and 2B (MEN-2B). We report the results obtained by RET mutation analysis of subjects living in Sardinia, an Italian island whose inhabitants display a peculiar genetic background due to geographic isolation and low immigration rate for several centuries. Design: Retrospective study reporting data on 67 patients referred during the last 5 years for RET analysis because affected by MTC or first degree relatives of MTC patients. Main outcome: Only three mutations were identified affecting codons 620 (exon 10), 634 (exon 11), and 804 (exon 14); surprisingly, the most prevalent mutation found was V804M (overall prevalence: 59%). This finding is quite different from previous studies carried out in other Caucasian and non-Caucasian populations, in which the frequency of the V804M mutation is consistently reported less than 5%. The phenotype associated to V804M mutation was mostly FMTC (16/17 cases = 94.1%), but in one case (5.9%) primary hyperparathyroidism was found, suggesting a MEN-2A. Conclusions: These results underline the importance of the genetic background in the distribution of RET mutations and should be taken into consideration when performing genetic evaluation of MTC patients.Keywords
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