Germline mutations of RET proto-oncogene exon 2 in iranian population with medullary thyroid carcinoma

Medullary thyroid carcinoma (MTC) accounts for 5-10% of all thyroid cancers andit is inherited in autosomal dominant pattern. Association of RET proto-oncogene mutations in exons 10-16 with MTC is well recognized. Since less attention has been paid to the study of other exons within the same gene, therefore, the aim of this study was to determine the frequency of germ line mutations in exon 2 of the RET proto-oncogene in patients with MTC in Iranian population.
There were 223 subjects (125 patients and 98 family members) were participated n this study. Genomic DNA was extracted using standard salting out/proteinase K method. The exon2 and exon-intron boundaries were amplified by using Polymerase Chain Reaction (PCR) and the direct DNA sequencing method was used for genotype analysis.
The nucleotide changes c135G>A/A45A (rs1800858) in exon 2 and c.337>A (rs2435351) and c.337흾>T (rs2505530) were found in intronic region of RET gene. Among patients and relatives, the most and least genotype and allele frequencies were c.337흾>T (rs2505530) and c135G>A/A45A (rs1800858), respectively. Also we did not find any significant correlation between detected nucleotide changes and disease phenotype, gender and ethnicity.
No mutation was detected leading to change in amino acid sequences in exon 2 or in exon-intron splice sites. However, further studies are recommended to identify the probable correlation between detected variations and presence or absence of other mutations in other RET main exons, and also to find haplotype association with the disease.