Multiple endocrine neoplasia.

Abstract

The recent chromosomal mapping of the genes for two different autosomal dominant inherited predispositions to multiple endocrine neoplasias promises to be a significant breakthrough for the understanding of the pathogenesis of such lesions. Multiple endocrine neoplasia type 1 (MEN1) associates primary hyperparathyroidism, lesions of the endocrine pancreas and pituitary adenomas. The first hint that the MEN1 gene is localized on chromosome 11 came from the finding of allele losses in MEN1 associated tumours. Subsequent genetic linkage analysis to restriction fragment length polymorphism (RFLP) markers assigned the gene to chromosome band 11q13. MEN2A is characterized by medullary thyroid carcinoma and phaeochromocytoma. The disease locus was localized to the centromeric region of chromosome 10 by genetic linkage. For both syndromes genetic linkage maps of the flanking regions have been established, and a set of RFLP markers is now available for premorbid identification of gene carriers in affected families. Analysis of allele losses showed that tumorigenesis of parathyroid and pancreatic lesions results from unmasking of a recessive mutation at the MEN1 locus, and by deletion mapping the tentative MEN1 region was restricted to a few million base pairs. In contrast, such losses appear to be relatively rare in MEN2A associated lesions.