Author/Editor		Zupan, Andrej; Glavač, Damjan
Title		The development of rapid and accurate screening test for RET hotspot somatic and germline mutations in MEN2 syndromes
Type		članek
Publication year		2015
ISSN		0014-4800 - Experimental and molecular pathology
Language		eng
Abstract		Medullary thyroid carcinoma (MTC) is a rare endocrine malignancy with distinctive features separating it from other thyroid cancers. Cancer may be sporadic or occur as a consequence of the hereditary syndrome called multiple endocrine neoplasia type 2 (MEN2) with three distinct phenotypes in MEN2A, MEN2B and FMTC. Each variant of MEN 2 results from different RET gene mutation, with a good genotype-phenotype correlation. Goal of the study was to develop a fast and accurate screening method for a reliable detection of hot-spot RET germline and sporadic tumor mutations. From a cohort of 191 patients with MTC and their relatives, 38 tested positive and 31 tested negative for a germline or somatic tumor RET mutation were selected. A positive HRM mutation pattern was detected in all mutation-positive patients and altogether the method was able to clearly differentiate between twenty different genotypes. A novel germline variant p. Ala639Thr was detected in MTC patient, which was determined to be likely benign. Analytical specificity was determined to be 98.6% and a sensitivity threshold was determined to be 30%. The fast and accurate HRM method reduces the turnaround time providing fast and important information, especially when targeted anti-tyrosine kinase therapy on tumor samples is considered. Overall, we developed a high-throughput, accurate and cost-effective approach for the detection of RET germline and sporadic tumor mutations.
Keywords		multiple endocrine neoplasia somatic and germline mutations MEN2 syndromes multiple endokrine neoplazije somatske in reproduktivne mutacije