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Loss of heterozygosity in 11q13-14 regions in gastric neuroendocrine tumors not associated with multiple endocrine neoplasia type 1 syndrome.
Lab Invest. 1999 Jun; 79(6):671-7.LI

Abstract

Loss of heterozygosity (LOH) at the MEN1 gene locus at 11q13 is commonly found in type II gastric carcinoid tumors, which are associated with multiple endocrine neoplasia type 1 (MEN-1). In contrast, information is scanty or absent for other types of gastric neuroendocrine tumors, represented by type I carcinoids (associated with chronic atrophic gastritis), type III (sporadic) carcinoids, and neuroendocrine carcinomas. Moreover, LOH analysis of the allelic region distal to the MEN1 gene, which is postulated to contain an additional tumor suppressor gene effective in MEN-1-associated and sporadic endocrine tumors, has never been performed. To clarify these issues, DNA extracted from archival tissue from 25 type I carcinoids, 4 type III carcinoids, and 2 neuroendocrine carcinomas was amplified by PCR, using primers for six polymorphic markers located on chromosome 11q13 (PYGM, D11S4946, and D11S913) and 11q14 (D11S916, D11S901, and D11S1365), for analysis of LOH. Allelic losses in the 11q13-14 region with at least two polymorphic markers were found in 12 of 25 (48%) type I carcinoids. When LOH was found in the 11q13 region, it was large and continuous and extended to the most telomeric marker investigated. In one tumor, retention of heterozygosity for markers in the MEN1 region and LOH for distal markers were observed. No LOH was found in three of four type III carcinoids. Large deletions in both the 11q13 and 11q14 regions were observed in both neuroendocrine carcinomas investigated. In conclusion, LOH in the 11q13-14 regions is frequently found in type I carcinoids and neuroendocrine carcinomas of the stomach, suggesting the involvement of the MEN1 gene and/or a more telomeric tumor suppressor gene in the pathogenesis of these non-MEN-1-associated neuroendocrine tumors. The low rate of LOH at 11q13-14 suggests the predominance of different genetic mechanisms in type III carcinoids, which also differ from other types of gastric carcinoids in the lack of a promoter role for gastrin.

Authors+Show Affiliations

Department of Pathology, University of Parma, Italy.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10378509

Citation

D'Adda, T, et al. "Loss of Heterozygosity in 11q13-14 Regions in Gastric Neuroendocrine Tumors Not Associated With Multiple Endocrine Neoplasia Type 1 Syndrome." Laboratory Investigation; a Journal of Technical Methods and Pathology, vol. 79, no. 6, 1999, pp. 671-7.
D'Adda T, Keller G, Bordi C, et al. Loss of heterozygosity in 11q13-14 regions in gastric neuroendocrine tumors not associated with multiple endocrine neoplasia type 1 syndrome. Lab Invest. 1999;79(6):671-7.
D'Adda, T., Keller, G., Bordi, C., & Höfler, H. (1999). Loss of heterozygosity in 11q13-14 regions in gastric neuroendocrine tumors not associated with multiple endocrine neoplasia type 1 syndrome. Laboratory Investigation; a Journal of Technical Methods and Pathology, 79(6), 671-7.
D'Adda T, et al. Loss of Heterozygosity in 11q13-14 Regions in Gastric Neuroendocrine Tumors Not Associated With Multiple Endocrine Neoplasia Type 1 Syndrome. Lab Invest. 1999;79(6):671-7. PubMed PMID: 10378509.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Loss of heterozygosity in 11q13-14 regions in gastric neuroendocrine tumors not associated with multiple endocrine neoplasia type 1 syndrome. AU - D'Adda,T, AU - Keller,G, AU - Bordi,C, AU - Höfler,H, PY - 1999/6/23/pubmed PY - 1999/6/23/medline PY - 1999/6/23/entrez SP - 671 EP - 7 JF - Laboratory investigation; a journal of technical methods and pathology JO - Lab Invest VL - 79 IS - 6 N2 - Loss of heterozygosity (LOH) at the MEN1 gene locus at 11q13 is commonly found in type II gastric carcinoid tumors, which are associated with multiple endocrine neoplasia type 1 (MEN-1). In contrast, information is scanty or absent for other types of gastric neuroendocrine tumors, represented by type I carcinoids (associated with chronic atrophic gastritis), type III (sporadic) carcinoids, and neuroendocrine carcinomas. Moreover, LOH analysis of the allelic region distal to the MEN1 gene, which is postulated to contain an additional tumor suppressor gene effective in MEN-1-associated and sporadic endocrine tumors, has never been performed. To clarify these issues, DNA extracted from archival tissue from 25 type I carcinoids, 4 type III carcinoids, and 2 neuroendocrine carcinomas was amplified by PCR, using primers for six polymorphic markers located on chromosome 11q13 (PYGM, D11S4946, and D11S913) and 11q14 (D11S916, D11S901, and D11S1365), for analysis of LOH. Allelic losses in the 11q13-14 region with at least two polymorphic markers were found in 12 of 25 (48%) type I carcinoids. When LOH was found in the 11q13 region, it was large and continuous and extended to the most telomeric marker investigated. In one tumor, retention of heterozygosity for markers in the MEN1 region and LOH for distal markers were observed. No LOH was found in three of four type III carcinoids. Large deletions in both the 11q13 and 11q14 regions were observed in both neuroendocrine carcinomas investigated. In conclusion, LOH in the 11q13-14 regions is frequently found in type I carcinoids and neuroendocrine carcinomas of the stomach, suggesting the involvement of the MEN1 gene and/or a more telomeric tumor suppressor gene in the pathogenesis of these non-MEN-1-associated neuroendocrine tumors. The low rate of LOH at 11q13-14 suggests the predominance of different genetic mechanisms in type III carcinoids, which also differ from other types of gastric carcinoids in the lack of a promoter role for gastrin. SN - 0023-6837 UR - https://www.unboundmedicine.com/medline/citation/10378509/Loss_of_heterozygosity_in_11q13_14_regions_in_gastric_neuroendocrine_tumors_not_associated_with_multiple_endocrine_neoplasia_type_1_syndrome_ L2 - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=linkout&SEARCH=10378509.ui DB - PRIME DP - Unbound Medicine ER -