| Abstrakt: |
Among the hereditary cancer syndromes, there is considerable inter- and intra-familial variability in expression. In order to assess genotype/phenotype correlations to allow appropriate treatment, large families have to be examined periodically over a long period of time using an extensive screening program. Since 1973, we have screened five large families with multiple endocrine neoplasia type 2A MEN2A. and familial medullary thyroid carcinoma (FMTC), also referred to as MTC-only), for MTC, pheochromocytoma, and parathyroid disease by clinical tests and imaging methods. In all these families, a germline mutation in the RET proto-oncogene could be identified. The disease phenotype associated with different mutations was compared among the different families. In 130 disease gent carriers, DNA analysis appeared to be highly reliable: there have been no false-positive or -negative diagnoses. The distinct course of disease in a family (aggressiveness of MTC, frequency of pheochromocytomas and parathyroid disease, cure rates, and life expectancy) depends on the specific RET gene mutation present. In contrast to the classical clinical tests, DNA analysis permits unambiguous identification of MEN2A gene carriers and enables preventive thyroidectomy. In all families with MTC and mutations in a cysteine codon of the RET proto-oncogene, screening for other endocrinopathies is mandatory, as these also occur in apparent FMTC families. Therefore, we suggest that MEN2A families should not be subclassified as MEN2A and FMTC, but rather according to their specific mutation in the RET protein, for example. MEN2A RET Cys634Arg. and MEN2A RET Cys618Ser. [ABSTRACT FROM AUTHOR] |
