RET proto-oncogene hotspot mutational screening among sporadic medullary thyroid carcinoma

Introduction: Medullary thyroid carcinoma (MTC) is one of the aggressive forms of thyroid cancer and occurs 75% as sporadic form. RET proto-oncogene mutations have an important role for diagnosis and confirming MTC. The aim of this study was detecting germline hot spot RET mutations in apparently sporadic MTC (sMTC) and assessing in their families.Material and methods: 159 apparently sMTC patients referred to this study. In order to be sure about sporadic form ofMTC, their relatives (n=65) were assessed. Genomic DNA was extracted from peripheral blood leucocytes and detection ofnucleotide changes in the RET exons (10, 11, 13-16) were analyzed by PCR and direct DNA sequencing methods.Results: In sMTC patients, nine different types of germline mutations were found in exons 10, 11, and 14, including C618S (n=3), C620G (n=1), and C620R (n=1) in exon 10 and C630Y (n=1), C634Y (n=1), C634R (n=4), C634S (n=1), and C634G (n=1) in exon 11. Two patients had V804M mutation in exon 14. There was no mutation in exons 13, 15 and 16. There wasno mutation in the all analyzed exons in the relative persons. The G691S/S904S haplotype was identified in 85 patients and33 relatives. Conclusion: Finding germline mutation in MTC patients without any information about the disease in their family, could help mutation detection in their offspring and maybe useful in MTC screening and management. Thus, It seems, molecular screening of the RET gene in sMTC patients should not be limited to somatic mutation

کلیدواژه ها:

Sporadic Medullary thyroid cancer ، RET proto-oncogene ، mutation screening ، hot spot