جهش هاي رايج در اگزون 10 پروتوآنكوژن RET در بيماران مبتلا به سرطان مدولاري تيروئيد

Common mutations in exon 10 of RET proto-oncogene in patients with medullar thyroid carcinoma

Aims: Medullary thyroid carcinoma accounts for 5-10% of total types of thyroid cancers. An important role of mutations in the RET proto-oncogene in MTC has been well identified. The purpose of this study was to determine the prevalence of seven common germ-line mutations of the RET proto-oncogene in exon 10 in Iranian MTC patients. Materials & Methods: This descriptive study was performed in year 2009-2010. The study population was 217 MTC patients and their first-degree relatives who were selected by simple sampling method. Genomic DNA content of peripheral blood was extracted according to standard salting out/Proteinase K method. Mutation detection in RET proto-oncogene in exon 10 was assessed through PCR-RFLP method. Results: In 217 individuals (Female: Male 1.4:1, mean age 33.4+15.8 years), 9 mutations were identified at codons 618 (7 mutations) and 620 (2 mutations) in RET proto-oncogene exon 10. The most common amino-acid change was Cys618Phe. In addition, no mutation was found in codon 611. Conclusion: The mutations frequency of the RET proto-oncogene in exon 10 is 6% in the studied population. Accordingly, existence of the common mutations in the RET proto-oncogene in all MTC patients and their families is recommended particularly in other exons (11,12,13,14, 15,16) with a direct DNA sequencing method. Keywords: Medullary Thyroid Carcinoma, RET Proto-oncogene, Germ-line Mutation, Exon 10