Clonality of parathyroid tumors in familial multiple endocrine neoplasia type 1.
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 less than 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 adenomas from patients without MEN-1, 9 showed similar allelic losses in chromosome 11; in 7 the losses included the apparent MEN-1 locus. We conclude that many "hyperplastic" parathyroid tumors in familial MEN-1 are in fact monoclonal and may progress or even begin to develop by inactivation of the MEN-1 gene (at 11q13) in a precursor cell. Some sporadic adenomas have allelic losses on chromosome 11, which may also involve the MEN-1 gene.
Friedman
E
E
Molecular Pathophysiology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Md.
Sakaguchi
K
K
Bale
A E
AE
Falchetti
A
A
Streeten
E
E
Zimering
M B
MB
Weinstein
L S
LS
McBride
W O
WO
Nakamura
Y
Y
Brandi
M L
ML
D000236:Adenoma / Q000235:genetics*; D000483:Alleles; D002872:Chromosome Deletion; D002880:Chromosomes, Human, Pair 11; D002999:Clone Cells; D006801:Humans; D006965:Hyperplasia; D009377:Multiple Endocrine Neoplasia / Q000235:genetics* / Q000473:pathology; D010282:Parathyroid Neoplasms / Q000235:genetics* / Q000473:pathology