Clonality of parathyroid tumors in familial multiple endocrine neoplasia type 1

E. Friedman, K. Sakaguchi, A. E. Bale, A. Falchetti, E. Streeten, M. B. Zimering, L. S. Weinstein, W. O. McBride, Y. Nakamura, M. L. Brandi, J. A. Norton, G. D. Aurbach, Allen M. Spiegel, S. J. Marx

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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 11q13) in a precursor cell. Some sporadic adenomas have allelic losses on chromosome 11, which may also involve the MEN-1 gene.

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

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Multiple Endocrine Neoplasia Type 1
Chromosomes, Human, Pair 11
Neoplasms
Adenoma
Loss of Heterozygosity
Alleles
Hyperplasia
Genes
Islets of Langerhans

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Friedman, E., Sakaguchi, K., Bale, A. E., Falchetti, A., Streeten, E., Zimering, M. B., ... Marx, S. J. (1989). Clonality of parathyroid tumors in familial multiple endocrine neoplasia type 1. New England Journal of Medicine, 321(4), 213-218.

Clonality of parathyroid tumors in familial multiple endocrine neoplasia type 1. / Friedman, E.; Sakaguchi, K.; Bale, A. E.; Falchetti, A.; Streeten, E.; Zimering, M. B.; Weinstein, L. S.; McBride, W. O.; Nakamura, Y.; Brandi, M. L.; Norton, J. A.; Aurbach, G. D.; Spiegel, Allen M.; Marx, S. J.

In: New England Journal of Medicine, Vol. 321, No. 4, 1989, p. 213-218.

Research output: Contribution to journalArticle

Friedman, E, Sakaguchi, K, Bale, AE, Falchetti, A, Streeten, E, Zimering, MB, Weinstein, LS, McBride, WO, Nakamura, Y, Brandi, ML, Norton, JA, Aurbach, GD, Spiegel, AM & Marx, SJ 1989, 'Clonality of parathyroid tumors in familial multiple endocrine neoplasia type 1', New England Journal of Medicine, vol. 321, no. 4, pp. 213-218.
Friedman E, Sakaguchi K, Bale AE, Falchetti A, Streeten E, Zimering MB et al. Clonality of parathyroid tumors in familial multiple endocrine neoplasia type 1. New England Journal of Medicine. 1989;321(4):213-218.
Friedman, E. ; Sakaguchi, K. ; Bale, A. E. ; Falchetti, A. ; Streeten, E. ; Zimering, M. B. ; Weinstein, L. S. ; McBride, W. O. ; Nakamura, Y. ; Brandi, M. L. ; Norton, J. A. ; Aurbach, G. D. ; Spiegel, Allen M. ; Marx, S. J. / Clonality of parathyroid tumors in familial multiple endocrine neoplasia type 1. In: New England Journal of Medicine. 1989 ; Vol. 321, No. 4. pp. 213-218.
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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 11q13) in a precursor cell. Some sporadic adenomas have allelic losses on chromosome 11, which may also involve the MEN-1 gene.",
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