Screening of six risk exons of the RET proto-oncogene in families with medullary thyroid carcinoma in the Czech Republic

Abstract

Medullary thyroid carcinoma (MTC) occurs as a sporadic form (75%) or as an autosomal dominant inherited familial disorder (25%) called familial MTC (FMTC) or as multiple endocrine neoplasia type 2 (MEN2) syndromes. Germ-line mutations in the rearranged during transfection (RET) proto-oncogene in exons 10, 11, 13, 14, 15 and 16 are known to be a cause of most of the familial forms. In this paper we report molecular genetic testing of 106 families with MTC (358 tested persons) from the Czech Republic in which we directly sequenced these six exons of the RET proto-oncogene. We detected germ-line mutations in 100% of MEN2B families (4/4 families), 90% of MEN2A families (9/10), 40% of FMTC families (4/10) and 7% of apparently sporadic MTC (6/82). Eleven different germ-line mutations were revealed. MEN2B was associated with mutation Met918 Thr in exon 16. In one MEN2B family beside this mutation the Tyr791 Phe was also found, which has not yet been reported. MEN2A was restricted to different mutations in exon 11 (codon 634). In FMTC and 'sporadic' MTC families the mutations in exons 10, 11, 13 and 14 were detected. The genotype/ phenotype correlations are given. Genetic testing revealed germ-line mutations in 23 index patients, 24 family members and excluded them in 53 relatives.

Genetic screening of patients with medullary thyroid cancer in a referral center in Greece during the past two decades

“…Table 2 The spectrum of RET mutations identified in families with hereditary medullary thyroid cancer in our center in Greece compared with those described by other European groups. The prevalence (n(%)) of each mutation is shown (data from references (8,20,22) Declaration of interest The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.…”

“…the Czech Republic they represent 21.7% (23/106) of MTC patients (20,25). The relevant percentage in Spain is 22.8% (26/114) (22).…”

“…Mutations in both exons 10 or 11 (Spain, Portugal, India, Saudi Arabia, Korea, and Czech Republic) and only 11 (Turkey and Taiwan) have been reported (16,17,18,19,20,21,22,23). Especially in the Czech Republic a higher than usual prevalence of mutations in exons 13 and 14 (17.45 and 13.0% respectively) has been reported (20).…”

Multiple endocrine neoplasia type 2A in two families with the familial medullary thyroid carcinoma associated G533C mutation of the RET proto-oncogene

“…Sequencing was performed in an ABI3100 genetic analyzer. The genetic protocol included the screening for RET mutations in exons 7-19 and 21, according to standard procedures (10)(11)(12)(13)(14).…”

“…MEN2 is caused by germline gain-of-function mutations of the RET proto-oncogene (RET) (2). Mutations affecting the cysteine-rich extracellular domain encoded in RET exons 10-15 have been associated with MEN2A; a single point mutation in RET exons 15 and 16 has been associated with MEN2B; mutations at certain codons in various exons of RET (5,8,(11)(12)(13)(14)(15)(16) have been associated with familial medullary thyroid carcinoma (FMTC) (1,(3)(4)(5)(6)(7). However, the G533C mutation in exon 8 of the RET is a rare mutation and has been mainly associated with FMTC (8).…”