Allelic deletions on chromosome 11q13 in multiple endocrine neoplasia type 1-associated and sporadic gastrinomas and pancreatic endocrine tumors

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

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Abstract

Endocrine tumors (ETs) of pancreas and duodenum occur sporadically and as a part of multiple endocrine neoplasia type i (MEN1). The MEN1 tumor suppressor gene has been localized to chromosome 11q13 by linkage analysis but has not yet isolated. Previous allelic deletion studies in enteropancreatic ETs suggested MEN1 gene involvement in tumorigenesis of familia pancreatic ETs (nongastrinomas) and sporadic gastrinomas. However, only a few MEN1-associated duodenal gastrinomas and sporadic pancreatic nongastrinomas have been investigated. We used tissue microdissection to analyze 95 archival pancreatic and duodenal ETs and metastases from 50 patients for loss of heterozygosity (LOH) on 11q13 with 10 polymorphic markers spanning the area of the putative MEN1 gene. Chromosome 11q13 LOH was detected in 23 of 27 (85%) MEN1-associated pancreatic ETs (nongastrinomas), 14 of 34 (41%) MEN1-associated gastrinomas, 3 of 16 (19%) sporadic insulinomas, and 8 of 18 (44%) sporadic gastrinomas. Analysis of LOH on 11q13 showed different deletion patterns in ETs from different MEN1 patients and in multiple tumors from individual MEN1 patients. The present results suggest that the MEN1 gene plays a role in all four tumor types. The lower rate of 11q13 LOH in MEN1-associated and sporadic gastrinomas and sporadic insulinomas as compared to MEN1 nongastrinomas may reflect alternative genetic pathways for the development of these tumors or mechanisms of the MEN1 gene inactivation that do not involve large deletions. The isolation of the MEN1 gene is necessary to further define its role in pathogenesis of pancreatic and duodenal ETs.

Original languageEnglish (US)
Pages (from-to)2238-2243
Number of pages6
JournalCancer Research
Volume57
Issue number11
StatePublished - Jun 1 1997
Externally publishedYes

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Gastrinoma
Multiple Endocrine Neoplasia Type 1
Chromosome Deletion
Neoplasms
Loss of Heterozygosity
Insulinoma
Genes
Chromosomes
Multiple Endocrine Neoplasia
Microdissection
Gene Silencing
Tumor Suppressor Genes
Islets of Langerhans

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Debelenko, L. V., Zhuang, Z., Emmert-Buck, M. R., Chandrasekharappa, S. C., Manickam, P., Guru, S. C., ... Lubensky, I. A. (1997). Allelic deletions on chromosome 11q13 in multiple endocrine neoplasia type 1-associated and sporadic gastrinomas and pancreatic endocrine tumors. Cancer Research, 57(11), 2238-2243.

Allelic deletions on chromosome 11q13 in multiple endocrine neoplasia type 1-associated and sporadic gastrinomas and pancreatic endocrine tumors. / Debelenko, Larisa V.; Zhuang, Zhengping; Emmert-Buck, Michael R.; Chandrasekharappa, Settara C.; Manickam, Pachiappan; Guru, Siradanahalli C.; Marx, Stephen J.; Skarulis, Monica C.; Spiegel, Allen M.; Collins, Francis S.; Jensen, Robert T.; Liotta, Lance A.; Lubensky, Irina A.

In: Cancer Research, Vol. 57, No. 11, 01.06.1997, p. 2238-2243.

Research output: Contribution to journalArticle

Debelenko, LV, Zhuang, Z, Emmert-Buck, MR, Chandrasekharappa, SC, Manickam, P, Guru, SC, Marx, SJ, Skarulis, MC, Spiegel, AM, Collins, FS, Jensen, RT, Liotta, LA & Lubensky, IA 1997, 'Allelic deletions on chromosome 11q13 in multiple endocrine neoplasia type 1-associated and sporadic gastrinomas and pancreatic endocrine tumors', Cancer Research, vol. 57, no. 11, pp. 2238-2243.
Debelenko LV, Zhuang Z, Emmert-Buck MR, Chandrasekharappa SC, Manickam P, Guru SC et al. Allelic deletions on chromosome 11q13 in multiple endocrine neoplasia type 1-associated and sporadic gastrinomas and pancreatic endocrine tumors. Cancer Research. 1997 Jun 1;57(11):2238-2243.
Debelenko, Larisa V. ; Zhuang, Zhengping ; Emmert-Buck, Michael R. ; Chandrasekharappa, Settara C. ; Manickam, Pachiappan ; Guru, Siradanahalli C. ; Marx, Stephen J. ; Skarulis, Monica C. ; Spiegel, Allen M. ; Collins, Francis S. ; Jensen, Robert T. ; Liotta, Lance A. ; Lubensky, Irina A. / Allelic deletions on chromosome 11q13 in multiple endocrine neoplasia type 1-associated and sporadic gastrinomas and pancreatic endocrine tumors. In: Cancer Research. 1997 ; Vol. 57, No. 11. pp. 2238-2243.
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abstract = "Endocrine tumors (ETs) of pancreas and duodenum occur sporadically and as a part of multiple endocrine neoplasia type i (MEN1). The MEN1 tumor suppressor gene has been localized to chromosome 11q13 by linkage analysis but has not yet isolated. Previous allelic deletion studies in enteropancreatic ETs suggested MEN1 gene involvement in tumorigenesis of familia pancreatic ETs (nongastrinomas) and sporadic gastrinomas. However, only a few MEN1-associated duodenal gastrinomas and sporadic pancreatic nongastrinomas have been investigated. We used tissue microdissection to analyze 95 archival pancreatic and duodenal ETs and metastases from 50 patients for loss of heterozygosity (LOH) on 11q13 with 10 polymorphic markers spanning the area of the putative MEN1 gene. Chromosome 11q13 LOH was detected in 23 of 27 (85{\%}) MEN1-associated pancreatic ETs (nongastrinomas), 14 of 34 (41{\%}) MEN1-associated gastrinomas, 3 of 16 (19{\%}) sporadic insulinomas, and 8 of 18 (44{\%}) sporadic gastrinomas. Analysis of LOH on 11q13 showed different deletion patterns in ETs from different MEN1 patients and in multiple tumors from individual MEN1 patients. The present results suggest that the MEN1 gene plays a role in all four tumor types. The lower rate of 11q13 LOH in MEN1-associated and sporadic gastrinomas and sporadic insulinomas as compared to MEN1 nongastrinomas may reflect alternative genetic pathways for the development of these tumors or mechanisms of the MEN1 gene inactivation that do not involve large deletions. The isolation of the MEN1 gene is necessary to further define its role in pathogenesis of pancreatic and duodenal ETs.",
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T1 - Allelic deletions on chromosome 11q13 in multiple endocrine neoplasia type 1-associated and sporadic gastrinomas and pancreatic endocrine tumors

AU - Debelenko, Larisa V.

AU - Zhuang, Zhengping

AU - Emmert-Buck, Michael R.

AU - Chandrasekharappa, Settara C.

AU - Manickam, Pachiappan

AU - Guru, Siradanahalli C.

AU - Marx, Stephen J.

AU - Skarulis, Monica C.

AU - Spiegel, Allen M.

AU - Collins, Francis S.

AU - Jensen, Robert T.

AU - Liotta, Lance A.

AU - Lubensky, Irina A.

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