The multiple endocrine neoplasia type I gene locus is involved in the pathogenesis of type II gastric carcinoids

L. V. Debelenko; M. R. Emmert-Buck; Z. Zhuang; E. Epshteyn; C. A. Moskaluk; R. T. Jensen; L. A. Liotta; I. A. Lubensky

doi:10.1016/S0016-5085(97)70171-9

The multiple endocrine neoplasia type I gene locus is involved in the pathogenesis of type II gastric carcinoids

L. V. Debelenko, M. R. Emmert-Buck, Z. Zhuang, E. Epshteyn, C. A. Moskaluk, R. T. Jensen, L. A. Liotta, I. A. Lubensky^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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Abstract

Background and Aims: Both gastrin and genetic factors were suggested to underlie the pathogenesis of multiple gastric enterochromaffin-like (ECL) cell carcinoids. To assess the role of genetic alterations in carcinoid tumorigenesis, loss of heterezygosity (LOH) at the locus of the multiple endocrine neoplasia type 1 (MEN1) gene was studied in gastric carcinoids of patients with MEN-1 and chronic atrophic type A gastritis (ACAG), as well as in sporadically arising intestinal carcinoids. Methods: DNA extracted from archival tissue sections of 35 carcinoid tumors was assessed for LOH with eight polymorphic markers on chromosome 11q13. A combined tumor and family study was performed in 1 patient with MEN-1-Zollinger-Ellison syndrome (ZES). Results: LOH at 11q13 loci was detected in 15 of 20 (75%) MEN-1-ZES carcinoids, and each ECL-cell carcinoid with LOH showed deletion of the wild- type allele. Only 1 of 6 A-CAG carcinoids displayed LOH at the MEN-1 gene locus, and none of the 9 intestinal and rectal carcinoids showed 11q13 LOH. Conclusions: Gastric ECL-cell carcinoid is an independent tumor type of MEN- 1 that shares a common developmental mechanism (via inactivation of the MEN- 1 gene) with entero-pancreatic and parathyroid MEN-1 tumors. Further analysis of sporadic and A-CAG carcinoids is needed to elucidate genetic factors involved in their tumorigenesis.

Original language	English
Pages (from-to)	773-781
Number of pages	9
Journal	Gastroenterology
Volume	113
Issue number	3
DOIs	https://doi.org/10.1016/S0016-5085(97)70171-9
State	Published - 1997
Externally published	Yes

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10.1016/S0016-5085(97)70171-9

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@article{34f4ff9a087a4773b27ec02672c02123,

title = "The multiple endocrine neoplasia type I gene locus is involved in the pathogenesis of type II gastric carcinoids",

abstract = "Background and Aims: Both gastrin and genetic factors were suggested to underlie the pathogenesis of multiple gastric enterochromaffin-like (ECL) cell carcinoids. To assess the role of genetic alterations in carcinoid tumorigenesis, loss of heterezygosity (LOH) at the locus of the multiple endocrine neoplasia type 1 (MEN1) gene was studied in gastric carcinoids of patients with MEN-1 and chronic atrophic type A gastritis (ACAG), as well as in sporadically arising intestinal carcinoids. Methods: DNA extracted from archival tissue sections of 35 carcinoid tumors was assessed for LOH with eight polymorphic markers on chromosome 11q13. A combined tumor and family study was performed in 1 patient with MEN-1-Zollinger-Ellison syndrome (ZES). Results: LOH at 11q13 loci was detected in 15 of 20 (75%) MEN-1-ZES carcinoids, and each ECL-cell carcinoid with LOH showed deletion of the wild- type allele. Only 1 of 6 A-CAG carcinoids displayed LOH at the MEN-1 gene locus, and none of the 9 intestinal and rectal carcinoids showed 11q13 LOH. Conclusions: Gastric ECL-cell carcinoid is an independent tumor type of MEN- 1 that shares a common developmental mechanism (via inactivation of the MEN- 1 gene) with entero-pancreatic and parathyroid MEN-1 tumors. Further analysis of sporadic and A-CAG carcinoids is needed to elucidate genetic factors involved in their tumorigenesis.",

author = "Debelenko, {L. V.} and Emmert-Buck, {M. R.} and Z. Zhuang and E. Epshteyn and Moskaluk, {C. A.} and Jensen, {R. T.} and Liotta, {L. A.} and Lubensky, {I. A.}",

note = "Funding Information: *Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland; ‡Department of Pathology, University of Virginia, Charlottesville, Virginia; and §Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland",

year = "1997",

doi = "10.1016/S0016-5085(97)70171-9",

language = "English",

volume = "113",

pages = "773--781",

journal = "Gastroenterology",

issn = "0016-5085",

publisher = "W.B. Saunders",

number = "3",

}

TY - JOUR

T1 - The multiple endocrine neoplasia type I gene locus is involved in the pathogenesis of type II gastric carcinoids

AU - Debelenko, L. V.

AU - Emmert-Buck, M. R.

AU - Zhuang, Z.

AU - Epshteyn, E.

AU - Moskaluk, C. A.

AU - Jensen, R. T.

AU - Liotta, L. A.

AU - Lubensky, I. A.

N1 - Funding Information: *Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland; ‡Department of Pathology, University of Virginia, Charlottesville, Virginia; and §Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland

PY - 1997

Y1 - 1997

N2 - Background and Aims: Both gastrin and genetic factors were suggested to underlie the pathogenesis of multiple gastric enterochromaffin-like (ECL) cell carcinoids. To assess the role of genetic alterations in carcinoid tumorigenesis, loss of heterezygosity (LOH) at the locus of the multiple endocrine neoplasia type 1 (MEN1) gene was studied in gastric carcinoids of patients with MEN-1 and chronic atrophic type A gastritis (ACAG), as well as in sporadically arising intestinal carcinoids. Methods: DNA extracted from archival tissue sections of 35 carcinoid tumors was assessed for LOH with eight polymorphic markers on chromosome 11q13. A combined tumor and family study was performed in 1 patient with MEN-1-Zollinger-Ellison syndrome (ZES). Results: LOH at 11q13 loci was detected in 15 of 20 (75%) MEN-1-ZES carcinoids, and each ECL-cell carcinoid with LOH showed deletion of the wild- type allele. Only 1 of 6 A-CAG carcinoids displayed LOH at the MEN-1 gene locus, and none of the 9 intestinal and rectal carcinoids showed 11q13 LOH. Conclusions: Gastric ECL-cell carcinoid is an independent tumor type of MEN- 1 that shares a common developmental mechanism (via inactivation of the MEN- 1 gene) with entero-pancreatic and parathyroid MEN-1 tumors. Further analysis of sporadic and A-CAG carcinoids is needed to elucidate genetic factors involved in their tumorigenesis.

AB - Background and Aims: Both gastrin and genetic factors were suggested to underlie the pathogenesis of multiple gastric enterochromaffin-like (ECL) cell carcinoids. To assess the role of genetic alterations in carcinoid tumorigenesis, loss of heterezygosity (LOH) at the locus of the multiple endocrine neoplasia type 1 (MEN1) gene was studied in gastric carcinoids of patients with MEN-1 and chronic atrophic type A gastritis (ACAG), as well as in sporadically arising intestinal carcinoids. Methods: DNA extracted from archival tissue sections of 35 carcinoid tumors was assessed for LOH with eight polymorphic markers on chromosome 11q13. A combined tumor and family study was performed in 1 patient with MEN-1-Zollinger-Ellison syndrome (ZES). Results: LOH at 11q13 loci was detected in 15 of 20 (75%) MEN-1-ZES carcinoids, and each ECL-cell carcinoid with LOH showed deletion of the wild- type allele. Only 1 of 6 A-CAG carcinoids displayed LOH at the MEN-1 gene locus, and none of the 9 intestinal and rectal carcinoids showed 11q13 LOH. Conclusions: Gastric ECL-cell carcinoid is an independent tumor type of MEN- 1 that shares a common developmental mechanism (via inactivation of the MEN- 1 gene) with entero-pancreatic and parathyroid MEN-1 tumors. Further analysis of sporadic and A-CAG carcinoids is needed to elucidate genetic factors involved in their tumorigenesis.

UR - http://www.scopus.com/inward/record.url?scp=0030820392&partnerID=8YFLogxK

U2 - 10.1016/S0016-5085(97)70171-9

DO - 10.1016/S0016-5085(97)70171-9

M3 - Article

C2 - 9287968

AN - SCOPUS:0030820392

SN - 0016-5085

VL - 113

SP - 773

EP - 781

JO - Gastroenterology

JF - Gastroenterology

IS - 3

ER -

The multiple endocrine neoplasia type I gene locus is involved in the pathogenesis of type II gastric carcinoids

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