title: Molecular analysis of the RET proto-oncogene key exons in patients with medullary thyroid carcinoma: a comprehensive study of the Iranian population.
abstract: BACKGROUND
  Germ-line mutations of RET proto-oncogene are the known cause of hereditary medullary thyroid carcinoma (MTC), which account for approximately 25% of all MTC cases and occur as multiple endocrine neoplasia type 2 syndromes. Here, we present the first comprehensive genetic screening and analysis of MTC among Iranian families.
  
  
  METHODS
  A total of 55 patients with MTC (male to female ratio=1:1.6; average age of disease onset = 33 ± 13 years) from 53 independent families participated in this study. All of the patients had undergone total thyroidectomy between 1999 and 2006, and 51 of them were clinically characterized as apparently sporadic cases. Genomic DNA samples were obtained and following highly-specific polymerase chain reaction amplification of the 6 RET key exons (10, 11, 13, 14, 15, and 16) were subjected to direct DNA sequencing without a requirement for a purification step.
  
  
  RESULTS
  Sequence analysis revealed that 9 (17.6%) of the apparently sporadic cases (from 8 kindreds) carried an RET germ-line mutation. Of the seven different mutations identified among all of the families studied, five were in the cysteine codons, with Cys634Arg having the highest prevalence (45.5%) among the afflicted families. Mutation carriers have an earlier age of onset (21 ± 6) versus the sporadic cases (37 ± 12).
  
  
  CONCLUSIONS
  This is the first comprehensive genetic screening and analysis of MTC among Iranian families. The results further confirm the need and advantages of DNA sequencing for identification of hereditary MTC cases. There does not seem to be a meaningful correlation between single nucleotide polymorphism patterns and the average age of disease onset. Geographical distribution of the sporadic cases, however, shows a significant concentration toward the Northern regions of the country, noticeably the provinces situated directly to the south of the Caspian Sea.
authors.affiliation: Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences (TUMS), Tehran, Iran.
authors.forename: Ehsan
authors.initials: E
authors.lastname: Alvandi
authors.forename: Seyed Mohammad
authors.initials: SM
authors.lastname: Akrami
authors.forename: Mohsen
authors.initials: M
authors.lastname: Chiani
authors.forename: Mehdi
authors.initials: M
authors.lastname: Hedayati
authors.forename: Babak Noori
authors.initials: BN
authors.lastname: Nayer
authors.forename: Mohammad Reza Mohajeri
authors.initials: MR
authors.lastname: Tehrani
authors.forename: Manouchehr
authors.initials: M
authors.lastname: Nakhjavani
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Pedram
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018276:Carcinoma, Medullary / Q000235:genetics*; D018278:Carcinoma, Neuroendocrine; D002648:Child; D005091:Exons / Q000235:genetics; D005260:Female; D005817:Genetic Counseling; D018095:Germ-Line Mutation; D006801:Humans; D007492:Iran; D008297:Male; D008875:Middle Aged; D018813:Multiple Endocrine Neoplasia Type 2a / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret