title: RET proto-oncogene in Sardinia: V804M is the most frequent mutation and may be associated with FMTC/MEN-2A phenotype.
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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
authors.affiliation: Endocrinology Unit, Department of Medical Science, University of Cagliari, Cagliari, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pinna
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Orgiana
authors.forename: Alessia
authors.initials: A
authors.lastname: Riola
authors.forename: Mariangela
authors.initials: M
authors.lastname: Ghiani
authors.forename: Maria Letizia
authors.initials: ML
authors.lastname: Lai
authors.forename: Carlo
authors.initials: C
authors.lastname: Carcassi
authors.forename: Stefano
authors.initials: S
authors.lastname: Mariotti
mesh_terms: D018276:Carcinoma, Medullary / Q000235:genetics*; D006801:Humans; D007558:Italy; D018813:Multiple Endocrine Neoplasia Type 2a / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D011519:Proto-Oncogenes; D013964:Thyroid Neoplasms / Q000235:genetics*
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret