Clonality of Parathyroid Tumors in Familial Multiple Endocrine Neoplasia Type 1

Eitan Friedman, Kazushige Sakaguchi, Allen E. Bale, Alberto Falchetti, Elizabeth Streeten, Mark B. Zimering, Lee S. Weinstein, Wesley O. Mcbride, Yusuke Nakamura, Maria Luisa Brandi, Jeffrey A. Norton, Gerald D. Aurbach, Allen M. Spiegel, Stephen J. Marx

Research output: Contribution to journalArticlepeer-review

268 Scopus citations

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 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 11ϥ13) in a precursor cell. Some sporadic adenomas have allelic losses on chromosome 11, which may also involve the MEN-1 gene. PRIMARY hyperparathyroidism is a common disorder caused either by an adenoma of a single parathyroid gland or by tumors, usually referred to as hyperplasia, of all four glands.1,2 Arnold et al.3 showed that at least six of eight sporadic parathyroid adenomas that they studied contained a large monoclonal component, on the basis of testing of DNA for X-chromosome-inactivation patterns and clonal rearrangements of the parathyroid hormone gene. Primary parathyroid hyperplasia is generally believed not to be represented as a monoclonal tumor4,5; indeed, analysis of DNA from five hyperplastic parathyroid glands did not suggest that a monoclonal component was present…

Original languageEnglish (US)
Pages (from-to)213-218
Number of pages6
JournalNew England Journal of Medicine
Volume321
Issue number4
DOIs
StatePublished - Jul 27 1989
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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