Clonality of Parathyroid Tumors in Familial Multiple Endocrine Neoplasia Type 1

Abstract Familial multiple endocrine neoplasia type 1 (MEN-1) is characterized by tumors of the parathyroids, endocrine pancreas, and anterior pituitary. Since the gene associated with MEN-1, located on chromosome 11 (11q13), may normally inhibit tumor proliferation, tumors could arise from inactivation of one or both of the alleles. However, parathyroid tumors in patients with MEN-1 have been considered to result from polyclonal hyperplasia. Using genetic probes, we tested parathyroid tumors for a monoclonal component, represented by a loss of alleles at any of eight loci along chromosome 11. Ten of 16 tumors from 14 patients with familial MEN-1 had losses of alleles from chromosome 11. Tumors with losses were larger than those without (1.6 vs. 0.2 g; P<0.002), suggesting that a monoclonal adenoma may develop after a phase of polyclonal hyperplasia. In 7 of 10 tumors, the subregion of loss was less than the full length of chromosome 11 but always included one copy of the MEN-1 locus. Of 34 sporadic adeno...