PRESYMPTOMATIC DNA SCREENING IN FAMILIES WITH MULTIPLE ENDOCRINE NEOPLASIA TYPE-2 AND FAMILIAL MEDULLARY-THYROID CARCINOMA

Background. Missense mutations of the ret proto-oncogene on chromosome 10q11.2 are the underlying cause of hereditary medullary thyroid carc inoma (MTC), either as familial MTC only (FMTC) or as a part of multip le endocrine neoplasia type 2 syndrome (MEN 2). This study presents ou r experience with direct presymptomatic DNA screening in MEN 2 and FMT C kindreds. Methods. Twenty one families with MEN 2 or FMTC were consi dered in the study. One hundred three individuals had been analyzed; 5 6 were at risk. The ret mutations were detected by DNA analysis of exo ns 10, 11, and 16 by using nonradioactive labeling method based on dig oxigenin DNA sequencing technique. Serum calcitonin evaluation was car ried out in all individuals at risk. Thyroidectomy was performed in th ose who had to undergo surgery. Results. The ret mutations were identi fied in all 21 families. In MEN 2A and FMTC families mutations occured in exons 10 and 11. MEN 2B families had mutations in exon 16. The mos t frequent mutation in MEN 2A and FMTC affected codon 634. Twenty one gene carriers were identified in unaffected individuals at risk. Ten o f 21 gene carriers had elevated calcitonin levels, and 11 had normal l evels, MTC or C-cell hyperplasia was found in six gene carriers with p athologic calcitonin values who underwent operation. In a 5-year-old g ene carrier with normal calcitonin values C-cell hyperplasia was evide nt. Conclusions. Direct predictive DNA analysis allows us to identify MEN 2 or FMTC gene carriers and offer them prophylactic treatment.