GENETIC TESTING IN PRESYMPTOMATIC DIAGNOSIS OF MULTIPLE ENDOCRINE NEOPLASIA

Multiple endocrine neoplasias (MEN) are familial diseases characterize d by endocrine neoplasms and transmitted in an autosomal dominant mann er. In MEN type I, the major lesions affect parathyroid glands, pancre atic islet cells and anterior pituitary. The MEN-I gene has been mappe d to chomosome 11q13 and a set of DNA-polymorphic markers localized cl ose to this region provides a useful tool for presymptomatic diagnosis in MEN-1 families. MEN type 2 refers to the inherited forms of medull ary thyroid carcinoma (MTC) associated or not with pheochromocytoma an d hyperparathyroidism. In MEN-2, germinal mutations of the C-RET proto -oncogene which is localized on chromosome 10q11 have been found in th e three clinical and allelic forms of the syndrome respectively, MEN-2 type A, B and familial isolated MTC. Mutations of C-RET are found in more than 90% of MEN-2 patients and genetic screening leads to accurat e risk evaluation in families and consequently a preventive treatment of MTC and adrenal neoplasms. Recent discoveries on MEN syndromes and related familial endocrine disorders have a major clinical impact and allow a better understanding of the physiological pathways involved in familial as well as in sporadic endocrine tumor pathogenesis.