Loss of heterozygosity at 11q13: Analysis of pituitary tumors, lung carcinoids, lipomas, and other uncommon tumors in subjects with familial multiple endocrine neoplasia type 1

Qihan Dong, Larisa V. Debelenko, Settara C. Chandrasekharappa, Michael R. Emmert-Buck, Zhengping Zhuang, Siradanahalli C. Guru, Pachiappan Manickam, Monica Skarulis, Irina A. Lubensky, Lance A. Liotta, Francis S. Collins, Stephen J. Marx, Allen M. Spiegel

Research output: Contribution to journalArticle

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Abstract

Loss of heterozygosity (LOH) for polymorphic markers flanking the multiple endocrine neoplasia type 1 (MEN-1) gene in parathyroid and pancreatic islet tumors from subjects with familial MEN-1 (FMEN-1) has been well documented and has led to the hypothesis that the MEN-1 gene functions as a tumor suppressor. To assess the role of the MEN-1 gene in the pathogenesis of tumors less commonly associated with MEN-1, we employed a large number of highly informative polymorphic markers closely linked to the MEN-1 gene to study a series of 13 such tumors from subjects with FMEN-1 for LOH at 11q13. We were able to identify LOH far 1 or more 11q13 markers in 2 of 3 pituitary tumors, 3 lung carcinoids, and 1 of 2 lipomas. In every case studied, the allele lost represented the normal allele inherited from the unaffected parent. No LOH was detected in 3 skin angiofibromas, an esophageal leiomyoma, or a renal angiomyolipoma despite the presence of at least 2 informative markers for each tumor. Our results suggest that, like that for parathyroid and pancreatic islet tumors, the pathogenesis of pituitary tumors, lung carcinoids, and lipomas occurring in subjects with FMEN-1 probably involves toss of the normal tumor suppressor function of the MEN-1 gene. Our inability to detect 11q13 LOH in skin angiofibromas, leiomyoma, and angiomyolipoma from subjects with FMEN-1 is consistent with the possibility that these neoplasms arose independently by a mechanism unrelated to the MEN- 1 gene, but a role for the MEN-1 gene in the pathogenesis of these tumors cannot be definitively excluded until the gene itself is identified and evaluated for small intragenic deletions or point mutations in such tumors.

Original languageEnglish (US)
Pages (from-to)1416-1420
Number of pages5
JournalJournal of Clinical Endocrinology and Metabolism
Volume82
Issue number5
StatePublished - 1997
Externally publishedYes

Fingerprint

Multiple Endocrine Neoplasia Type 1
Lipoma
Loss of Heterozygosity
Carcinoid Tumor
Pituitary Neoplasms
Tumors
Lung
Genes
Neoplasms
Angiofibroma
Angiomyolipoma
Leiomyoma
Skin
Islets of Langerhans
Alleles
Tumor Biomarkers
Sequence Deletion
Point Mutation

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Loss of heterozygosity at 11q13 : Analysis of pituitary tumors, lung carcinoids, lipomas, and other uncommon tumors in subjects with familial multiple endocrine neoplasia type 1. / Dong, Qihan; Debelenko, Larisa V.; Chandrasekharappa, Settara C.; Emmert-Buck, Michael R.; Zhuang, Zhengping; Guru, Siradanahalli C.; Manickam, Pachiappan; Skarulis, Monica; Lubensky, Irina A.; Liotta, Lance A.; Collins, Francis S.; Marx, Stephen J.; Spiegel, Allen M.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 82, No. 5, 1997, p. 1416-1420.

Research output: Contribution to journalArticle

Dong, Q, Debelenko, LV, Chandrasekharappa, SC, Emmert-Buck, MR, Zhuang, Z, Guru, SC, Manickam, P, Skarulis, M, Lubensky, IA, Liotta, LA, Collins, FS, Marx, SJ & Spiegel, AM 1997, 'Loss of heterozygosity at 11q13: Analysis of pituitary tumors, lung carcinoids, lipomas, and other uncommon tumors in subjects with familial multiple endocrine neoplasia type 1', Journal of Clinical Endocrinology and Metabolism, vol. 82, no. 5, pp. 1416-1420.
Dong, Qihan ; Debelenko, Larisa V. ; Chandrasekharappa, Settara C. ; Emmert-Buck, Michael R. ; Zhuang, Zhengping ; Guru, Siradanahalli C. ; Manickam, Pachiappan ; Skarulis, Monica ; Lubensky, Irina A. ; Liotta, Lance A. ; Collins, Francis S. ; Marx, Stephen J. ; Spiegel, Allen M. / Loss of heterozygosity at 11q13 : Analysis of pituitary tumors, lung carcinoids, lipomas, and other uncommon tumors in subjects with familial multiple endocrine neoplasia type 1. In: Journal of Clinical Endocrinology and Metabolism. 1997 ; Vol. 82, No. 5. pp. 1416-1420.
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abstract = "Loss of heterozygosity (LOH) for polymorphic markers flanking the multiple endocrine neoplasia type 1 (MEN-1) gene in parathyroid and pancreatic islet tumors from subjects with familial MEN-1 (FMEN-1) has been well documented and has led to the hypothesis that the MEN-1 gene functions as a tumor suppressor. To assess the role of the MEN-1 gene in the pathogenesis of tumors less commonly associated with MEN-1, we employed a large number of highly informative polymorphic markers closely linked to the MEN-1 gene to study a series of 13 such tumors from subjects with FMEN-1 for LOH at 11q13. We were able to identify LOH far 1 or more 11q13 markers in 2 of 3 pituitary tumors, 3 lung carcinoids, and 1 of 2 lipomas. In every case studied, the allele lost represented the normal allele inherited from the unaffected parent. No LOH was detected in 3 skin angiofibromas, an esophageal leiomyoma, or a renal angiomyolipoma despite the presence of at least 2 informative markers for each tumor. Our results suggest that, like that for parathyroid and pancreatic islet tumors, the pathogenesis of pituitary tumors, lung carcinoids, and lipomas occurring in subjects with FMEN-1 probably involves toss of the normal tumor suppressor function of the MEN-1 gene. Our inability to detect 11q13 LOH in skin angiofibromas, leiomyoma, and angiomyolipoma from subjects with FMEN-1 is consistent with the possibility that these neoplasms arose independently by a mechanism unrelated to the MEN- 1 gene, but a role for the MEN-1 gene in the pathogenesis of these tumors cannot be definitively excluded until the gene itself is identified and evaluated for small intragenic deletions or point mutations in such tumors.",
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T2 - Analysis of pituitary tumors, lung carcinoids, lipomas, and other uncommon tumors in subjects with familial multiple endocrine neoplasia type 1

AU - Dong, Qihan

AU - Debelenko, Larisa V.

AU - Chandrasekharappa, Settara C.

AU - Emmert-Buck, Michael R.

AU - Zhuang, Zhengping

AU - Guru, Siradanahalli C.

AU - Manickam, Pachiappan

AU - Skarulis, Monica

AU - Lubensky, Irina A.

AU - Liotta, Lance A.

AU - Collins, Francis S.

AU - Marx, Stephen J.

AU - Spiegel, Allen M.

PY - 1997

Y1 - 1997

N2 - Loss of heterozygosity (LOH) for polymorphic markers flanking the multiple endocrine neoplasia type 1 (MEN-1) gene in parathyroid and pancreatic islet tumors from subjects with familial MEN-1 (FMEN-1) has been well documented and has led to the hypothesis that the MEN-1 gene functions as a tumor suppressor. To assess the role of the MEN-1 gene in the pathogenesis of tumors less commonly associated with MEN-1, we employed a large number of highly informative polymorphic markers closely linked to the MEN-1 gene to study a series of 13 such tumors from subjects with FMEN-1 for LOH at 11q13. We were able to identify LOH far 1 or more 11q13 markers in 2 of 3 pituitary tumors, 3 lung carcinoids, and 1 of 2 lipomas. In every case studied, the allele lost represented the normal allele inherited from the unaffected parent. No LOH was detected in 3 skin angiofibromas, an esophageal leiomyoma, or a renal angiomyolipoma despite the presence of at least 2 informative markers for each tumor. Our results suggest that, like that for parathyroid and pancreatic islet tumors, the pathogenesis of pituitary tumors, lung carcinoids, and lipomas occurring in subjects with FMEN-1 probably involves toss of the normal tumor suppressor function of the MEN-1 gene. Our inability to detect 11q13 LOH in skin angiofibromas, leiomyoma, and angiomyolipoma from subjects with FMEN-1 is consistent with the possibility that these neoplasms arose independently by a mechanism unrelated to the MEN- 1 gene, but a role for the MEN-1 gene in the pathogenesis of these tumors cannot be definitively excluded until the gene itself is identified and evaluated for small intragenic deletions or point mutations in such tumors.

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