Allelic deletions on chromosome 11q13 in multiple tumors from individual MEN1 patients

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

Research output: Contribution to journalArticle

124 Citations (Scopus)

Abstract

Familial multiple endocrine neoplasia type 1 is an autosomal dominant hereditary disorder characterized by multiple parathyroid, pancreatic, duodenal and pituitary tumors. The parathyroid tumors may arise as diffuse areas of hyperplasia, whereas the pancreatic and duodenal tumors usually form as discrete nodules. Except for a single report, tumor loss of heterozygosity (LOH) slapping of the putative MEN1 suppressor gene on chromosome 11q13 in the past has been restricted by analysis of a single tumor from individual patients and somatic cellular contamination. For this reason, it has not been possible to analyze the clonality of the emerging MEN1 neoplasms. Furthermore, it has been previously unknown whether the LOH pattern varies between individual MEN1 tumors in a given patient or among tumors of different histological origins within unrelated patients. To address these previous limitations, the present study introduces a refinement in microdissection in which endothelial cells are stained and selectively excluded. Tissue microdissection was applied to study LOH patterns on chromosome 11q13 using 8 polymorphic DNA markers in 44 different MEN1 tumors from parathyroid, pancreas, and duodenum in nine unrelated patients. In addition, X-chromosome inactivation clonal analysis was applied to 16 individual microdissected regions from seven parathyroid glands in three female patients. The LOH rates of parathyroid lesions (100%) and endocrine tumors of the pancreas (83%) were strikingly different from the LOH rate of gastrinomas (21%), suggesting that the mechanism that drives LOH may be influenced by the tissue context. Moreover, combined LOH and X-chromosome inactivation scoring of the same microdissected region revealed that parathyroid MEN1 neoplasms can consist of more than use clone. In this study, the centromeric boundary of the putative MEN1 gene was PYGM. Analysis of differential LOH patterns in multiple microdissected tumors in the same patient constitutes a novel approach to suppressor gene mapping.

Original languageEnglish (US)
Pages (from-to)5272-5278
Number of pages7
JournalCancer Research
Volume56
Issue number22
StatePublished - Nov 15 1996
Externally publishedYes

Fingerprint

Multiple Endocrine Neoplasia Type 1
Chromosome Deletion
Loss of Heterozygosity
Neoplasms
Suppressor Genes
X Chromosome Inactivation
Microdissection
Chromosomes
Gastrinoma
Parathyroid Neoplasms
Parathyroid Glands
Chromosome Mapping
Pituitary Neoplasms
Islets of Langerhans
Genetic Markers
Duodenum
Hyperplasia
Pancreas
Endothelial Cells
Clone Cells

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Lubensky, I. A., Debelenko, L. V., Zhuang, Z., Emmert-Buck, M. R., Dong, Q., Chandrasekharappa, S., ... Liotta, L. A. (1996). Allelic deletions on chromosome 11q13 in multiple tumors from individual MEN1 patients. Cancer Research, 56(22), 5272-5278.

Allelic deletions on chromosome 11q13 in multiple tumors from individual MEN1 patients. / Lubensky, Irina A.; Debelenko, Larisa V.; Zhuang, Zhengping; Emmert-Buck, Michael R.; Dong, Qihan; Chandrasekharappa, Settara; Guru, Siradanahalli C.; Manickam, Pachiappan; Olufemi, Shodimu Emmanuel; Marx, Stephen J.; Spiegel, Allen M.; Collins, Francis S.; Liotta, Lance A.

In: Cancer Research, Vol. 56, No. 22, 15.11.1996, p. 5272-5278.

Research output: Contribution to journalArticle

Lubensky, IA, Debelenko, LV, Zhuang, Z, Emmert-Buck, MR, Dong, Q, Chandrasekharappa, S, Guru, SC, Manickam, P, Olufemi, SE, Marx, SJ, Spiegel, AM, Collins, FS & Liotta, LA 1996, 'Allelic deletions on chromosome 11q13 in multiple tumors from individual MEN1 patients', Cancer Research, vol. 56, no. 22, pp. 5272-5278.
Lubensky IA, Debelenko LV, Zhuang Z, Emmert-Buck MR, Dong Q, Chandrasekharappa S et al. Allelic deletions on chromosome 11q13 in multiple tumors from individual MEN1 patients. Cancer Research. 1996 Nov 15;56(22):5272-5278.
Lubensky, Irina A. ; Debelenko, Larisa V. ; Zhuang, Zhengping ; Emmert-Buck, Michael R. ; Dong, Qihan ; Chandrasekharappa, Settara ; Guru, Siradanahalli C. ; Manickam, Pachiappan ; Olufemi, Shodimu Emmanuel ; Marx, Stephen J. ; Spiegel, Allen M. ; Collins, Francis S. ; Liotta, Lance A. / Allelic deletions on chromosome 11q13 in multiple tumors from individual MEN1 patients. In: Cancer Research. 1996 ; Vol. 56, No. 22. pp. 5272-5278.
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abstract = "Familial multiple endocrine neoplasia type 1 is an autosomal dominant hereditary disorder characterized by multiple parathyroid, pancreatic, duodenal and pituitary tumors. The parathyroid tumors may arise as diffuse areas of hyperplasia, whereas the pancreatic and duodenal tumors usually form as discrete nodules. Except for a single report, tumor loss of heterozygosity (LOH) slapping of the putative MEN1 suppressor gene on chromosome 11q13 in the past has been restricted by analysis of a single tumor from individual patients and somatic cellular contamination. For this reason, it has not been possible to analyze the clonality of the emerging MEN1 neoplasms. Furthermore, it has been previously unknown whether the LOH pattern varies between individual MEN1 tumors in a given patient or among tumors of different histological origins within unrelated patients. To address these previous limitations, the present study introduces a refinement in microdissection in which endothelial cells are stained and selectively excluded. Tissue microdissection was applied to study LOH patterns on chromosome 11q13 using 8 polymorphic DNA markers in 44 different MEN1 tumors from parathyroid, pancreas, and duodenum in nine unrelated patients. In addition, X-chromosome inactivation clonal analysis was applied to 16 individual microdissected regions from seven parathyroid glands in three female patients. The LOH rates of parathyroid lesions (100{\%}) and endocrine tumors of the pancreas (83{\%}) were strikingly different from the LOH rate of gastrinomas (21{\%}), suggesting that the mechanism that drives LOH may be influenced by the tissue context. Moreover, combined LOH and X-chromosome inactivation scoring of the same microdissected region revealed that parathyroid MEN1 neoplasms can consist of more than use clone. In this study, the centromeric boundary of the putative MEN1 gene was PYGM. Analysis of differential LOH patterns in multiple microdissected tumors in the same patient constitutes a novel approach to suppressor gene mapping.",
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AU - Dong, Qihan

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AU - Guru, Siradanahalli C.

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AU - Olufemi, Shodimu Emmanuel

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