Genetic screening of patients with Medullary Thyroid Cancer (MTC) in a referral center in Greece during the past two decades.

Sarika L1, Papathoma A2, Garofalaki M3, Saltiki K4, Pappa T5, Pazaitou-Panayiotou K6, Anastasiou E7, Alevizaki M8.

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Abstract

Objective. Mutations in the RET gene, responsible for hereditary MTC vary between ethnic groups. We report the spectrum of mutations detected in patients with MTC in a referral centre in Greece. Patients and Methods. Screening for RET mutations was performed in 313 subjects from 188 unrelated families. 51 patients had clinical suspicion for MEN2, 133 were apparently sporadic, 4 had C Cell Hyperplasia (CCH) and 125 were family members. Exons 8, 10, 11, 13, 14, 15 and 16 were screened. Results. 58 individuals (30.8%) were RET mutations carriers, 120 (63.8 %) were classified as sporadic, 13 apparently sporadic (9.8%) were identified with RET mutation: ten carried the 533 mutation, exon 8 (previous reported), two the 804 mutation, exon 14 and one the 768 mutation, exon 13. Six patients (3.3%) with clinical features of MEN2A and negative for RET mutations were classified as unknown cause. Mutations of hereditary cases were: twenty one cases (36.2%) exon 8 codon G533C, nineteen (32.8%) exon 11 codon 634, nine (15.5%) exon 10, five (8.6%) exon 16, three (5.2%) exon 14 codon 804 and one exon 13, codon 768 (1.7%). Conclusion The spectrum of RET mutations in Greece differs from that in other populations and the prevalence of familial cases is higher. Mutation in exon 8 (Gly533Cys) was the most prevalent in familial cases unlike other series, followed by exon 11 (codon 634) mutations which are the most frequent elsewhere. Wide application of genetic screening in MTC reveals new molecular defects and helps characterize the spectrum of mutations in each ethnic group.