title: RET proto-oncogene mutations are restricted to codon 618 in Cypriot families with multiple endocrine neoplasia 2.
abstract: BACKGROUND
  RET germline mutations predispose to the development of inherited cancer syndrome multiple endocrine neoplasia type 2 (MEN2). Several variants of the RET proto-oncogene including G691S and S904S have been suggested to act as genetic modifiers at the age of onset ofMEN2.
  
  
  OBJECTIVE
  The aim of this study is to characterize clinically and molecularly 7 Cypriot patients with familial medullary thyroid carcinoma (FMTC) and 1 with MEN2A and also to determine the allelic frequencies of the RET variants G691S and S904S.
  
  
  METHODS
  Seven probands from FMTC families and 1 from MEN2A were screened for the presence of RET mutations and the G691S and S904S variants. Additionally, 226 healthy Cypriots, who served as controls were analysed in an attempt to compare the frequencies of G691S and S904S RET variants to those observed in the 8 patients.
  
  
  RESULTS
  The clinical diagnosis of the probands was based on clinical presentation and supported with biochemical findings. The germline C618R mutation of exon 10 was identified in all 8 probands and in 15 relatives from 7 different families. No significant difference in the G691S/S904S variants allele frequencies between patients (4/16 or 25%) and controls (124/452 or 27.4%) was found.
  
  
  CONCLUSIONS
  Mutational screening of the RET gene identified a common mutation (C618R) in all 8 (7 FMTC and 1 MEN2A) unrelated Cypriot patients which may be explained by a founder effect. Additionally, no association of the G691S/S904S variants was linked with the disease.
authors.affiliation: Department of Molecular Genetics, Function and Therapy, Cyprus Institute of Neurology and Genetics, P.O. Box 23462, 1683 Nicosia, Cyprus.
authors.forename: V
authors.initials: V
authors.lastname: Neocleous
authors.forename: N
authors.initials: N
authors.lastname: Skordis
authors.forename: G
authors.initials: G
authors.lastname: Portides
authors.forename: E
authors.initials: E
authors.lastname: Efstathiou
authors.forename: C
authors.initials: C
authors.lastname: Costi
authors.forename: N
authors.initials: N
authors.lastname: Ioannou
authors.forename: M
authors.initials: M
authors.lastname: Pantzaris
authors.forename: V
authors.initials: V
authors.lastname: Anastasiadou
authors.forename: C
authors.initials: C
authors.lastname: Deltas
authors.forename: L A
authors.initials: LA
authors.lastname: Phylactou
mesh_terms: D000328:Adult; D018276:Carcinoma, Medullary / Q000151:congenital; D002648:Child; D003535:Cyprus; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008297:Male; D008875:Middle Aged; D018813:Multiple Endocrine Neoplasia Type 2a / Q000235:genetics*; D009386:Neoplastic Syndromes, Hereditary / Q000235:genetics* / Q000601:surgery; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D011519:Proto-Oncogenes / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000601:surgery; D013965:Thyroidectomy
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret