Endocrine Abstracts

Introduction: Thyroid cancer is the most common endocrine cancer and medullary thyroid carcinoma (MTC) is one of the most malignant thyroid tumours which occur in both hereditary (25%) and sporadic (75%) forms. Mutations of the RET proto-oncogene in MTC development have been well demonstrated. The aim of the study was to investigate the mutational spectrum of exons 3, 5, 8, and 10–18 of RET proto-oncogene in MTC patients.

Material and methods: This retrospective study has been started since 2001 in Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, and Tehran, Iran. 399 participants, including 233 patients (176 sMTC, 40 FMTC, eight MEN2A, four MEN2B, five pheochromocitoma), and 166 relatives were evaluated. Genomic DNA was extracted by the standard Salting Out/ProteinaseK method and Mutation detection was performed through direct DNA sequencing. Sequence analysis was performed by Chromas Software version 2.3.

Results: Totally, in 233 patients (131 female, 102 male) and 166 relatives (91 female, 75 male), 82 mutations were identified in RET main exons, including 10, 11, and 13–16. Furthermore, 282 single nucleotide polymorphism (SNP) were found in exons 3, 13, and 14. Interestingly, G691S SNP and S904S SNP were 100% in linkage disequilibrium in 131 patients and 87 relatives. The most common mutation in our population were C634Y and C634R (4%) whereas C618R, C618S, C620G, L887L mutations had rare allele frequency (0.3%). Moreover, R886Q mutation was detected in exon 15 in two members of a family affected with MTC for the first time.

Discussion: Exon 11 and after that exon 10 were the most frequently mutated exons of RET proto-oncogene in MTC patients in Iranian population. As about half of patients with the hot spot mutations had the G691S/S904S haplotype simultaneously, further analysis needs for clarifying the effect of multiple risk alleles in MTC development.