Medullary thyroid cancer accounts for 5-10% of thyroid carcinomas. RET proto-oncogene mutations occur in all of the hereditary MTCs and about 66% of the sporadic MTCs. So, the detection of the RET mutations is necessary for rapid and proper diagnosis and treatment. This systematic review seeks to find a comprehensive list of RET gene mutations in the diagnosis of medullary thyroid cancer.
The previous studies on RET proto-oncogene mutations in the diagnosis of medullary thyroid cancer were searched in the major databases including PubMed, Scopus, Medline, Embase and NCBI between 2010 and 2021.
Missense mutations in exons 10, 11, 13, 14, 15, and 16 of the RET proto-oncogene have the highest frequency in MTCs. The most common mutations in FMTC, are in codons 609, 611, 618, and 620 in exon 10, codon 768 in exon 13, codon 804 in exon 14, and codon 634 in exon 11. In the case of MEN2A, RET gene mutations have been observed in exons 5, 8, 10, 11, with the highest mutations in exons 10 (codons 609, 611, 618, and 620) and exon 11 (codons 630 and 634). Moreover, M918T mutation in exon 16 and A883F mutation in exon 15 have been detected in 95% and 5% of the patients with MEN2B respectively. In the case of MTC, the M918T mutation in exon 16 is the most common mutation, which is associated with a poor prognosis. RET genetic screening is crucial for an exact approach to the diagnosis and treatment of MTC. Anyone with MTC, even without a family history of MEN2, should be genetically tested for the RET mutations to confirm or rule out the inherited disease and, if necessary, preventive thyroidectomy. This systematic review provided a comprehensive list of the reported mutations in the RET gene for the diagnosis of medullary thyroid cancer.
