Onkologija (May 2020)
RET proto-oncogene mutations in the Slovenian population of patients with medullary thyroid cancer
Abstract
Background. Medullary thyroid cancer (MTC) is a rare, endocrine tumour that occurs as part of hereditary cancer syndrome in approximately 25% of cases and develops as a sporadic form in 75%. The aim of the study was to evaluate the frequency and type of RET mutation occurrence in the Slovenian population between 1995 and 2015. Methods. A retrospective analysis of the National Cancer Registry of the Republic of Slovenia and the Registry of Patients with MTC of the Institute of Oncology in Ljubljana between 1995 and 2015 was made. The data of 143 patients with confirmed MTC and 43 healthy relatives referred to genetic counselling and testing was analyzed. Genomic DNA was isolated from peripheral blood leukocytes. Exons 10, 11, 13, 14, 15 and 16 of the RET proto-oncogene were amplified in the polymerase chain reaction (PCR). Point mutations of the RET gene were detected by single strand confirmation analysis (SSCA) and DNA sequencing. Detected mutations were confirmed by restriction enzymes. Results. A germline mutation in the RET proto-oncogene was identified in 51 individuals, 37 among them were patients with MTC, which accounts for 25.9% of all patients with MTC. Eight different germline RET mutations were found. Codons 634 and 618 were the most frequently altered codons, followed by codon 790, codon 804 and codon 918. The average crude incidence rate of MTC (between 1995 and 2015) is 0.34 per 100,000. Conclusions. We estimated that the crude incidence rate of MTC in Slovenia is 0.34 per 100,000. We discovered that 25.9% of Slovenian patients with MTC are RET mutation carriers. The most common mutations were found on codons 634 and 618.
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