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

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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.

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Debelenko, L. V., Emmert-Buck, M. R., Zhuang, Z., Epshteyn, E., Moskaluk, C. A., Jensen, R. T., … Lubensky, I. A. (1997). The multiple endocrine neoplasia type I gene locus is involved in the pathogenesis of type II gastric carcinoids. Gastroenterology, 113(3), 773–781. https://doi.org/10.1016/S0016-5085(97)70171-9

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