title: Haplotype Frequency of G691S/S904S in the RET Proto-Onco-gene in Patients with Medullary Thyroid Carcinoma.
abstract: BACKGROUND
  Medullary thyroid carcinoma (MTC) occurs in both sporadic (75%) and hereditary (25%) forms. The missense mutations of the REarranged during Transfection (RET) proto-oncogene in MTC development have been well demonstrated. The aim of this study was to investigate frequency of G691S/S904S haplotype in MTC patients and their relatives.
  
  
  METHODS
  In this research 293 participants were studied, including 181 patients (102 female, 79 male) and 112 their relatives (58 female, 54 male). Genomic DNA was extracted from peripheral blood leucocytes using the standard Salting Out/Proteinase K method. Nucleotide change detection was performed using PCR and direct DNA sequencing methods.
  
  
  RESULTS
  According to DNA sequencing results, 159 individuals (104 patients, 55 relatives) had both G691S (rs1799939) missense mutation in exon11 and S904S (rs1800863) synonymous mutation in exon 15 of RET proto-oncogene. The allele frequency of G691S/S904S haplotype was 21.15% in patients and 10.75% in their relatives.
  
  
  CONCLUSIONS
  The obtained data showed the frequency of G691S/S904S RET gene haplotype among Iranian MTC patients and their relatives. The G691S and S904S nucleotide changes were in complete linkage disequilibrium, so the results were grouped together and referred to as G691S/S904S haplotype. Further analysis is need to demonstrate the association between this haplotype and MTC development.
authors.affiliation: Cellular and Molecular Research Center, Research Institute for Endocrine Sciences, Obesity Research Center, Shahid Beheshti University of Medical sciences , Tehran, Iran.
authors.forename: Sara
authors.initials: S
authors.lastname: Sheikholeslami
authors.affiliation: Cellular and Molecular Research Center, Research Institute for Endocrine Sciences, Obesity Research Center, Shahid Beheshti University of Medical sciences , Tehran, Iran.
authors.forename: Marjan
authors.initials: M
authors.lastname: Zarif Yeganeh
authors.affiliation: Cellular and Molecular Research Center, Research Institute for Endocrine Sciences, Obesity Research Center, Shahid Beheshti University of Medical sciences , Tehran, Iran.
authors.forename: Laleh
authors.initials: L
authors.lastname: Hoghooghi Rad
authors.affiliation: Cellular and Molecular Research Center, Research Institute for Endocrine Sciences, Obesity Research Center, Shahid Beheshti University of Medical sciences , Tehran, Iran.
authors.forename: Hoda
authors.initials: H
authors.lastname: Golab Ghadaksaz
authors.affiliation: Cellular and Molecular Research Center, Research Institute for Endocrine Sciences, Obesity Research Center, Shahid Beheshti University of Medical sciences , Tehran, Iran.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Hedayati
keywords: G691S/S904S haplotype; Medullary; RET proto-oncogene; Thyroid cancer