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Survey of genetic alterations in gastrinomas.
Cancer Res. 2000 Oct 01; 60(19):5536-42.CR

Abstract

Gastrinomas are rare gastrin-secreting endocrine tumors that usually arise in the duodenum or pancreas and, if untreated, can cause severe peptic ulcers or metastatic disease. Although most tumors are sporadic they are especially common in patients with multiple endocrine neoplasia type 1 (MEN1), and most studies of these tumors have focused on the role of the MEN1 gene. Although the gene is commonly altered in sporadic tumors, this finding is not universal, and it is highly likely that other genetic defects play a significant role. In the present study, an in-depth analysis of the DNA of eight tumors was carried out in an effort to localize these areas. The experiments consisted of an analysis of 400 microsatellite marker loci distributed evenly throughout the human genome, and the results were confirmed with comparative genomic hybridization. Whereas deletions encompassing the MEN1 gene were seen in two tumors, the most striking result was multiple large rearrangements on chromosome 1 in two of the tumors with hepatic metastases. In several instances, an individual tumor had abnormalities of every informative maker on a given chromosome, presumably as a result of aneuploidy affecting that chromosome. Such defects were only seen in the four large or aggressive tumors, and the total number of chromosomes affected in a tumor ranged from 1 to a high of 13 in a patient who had an unusually aggressive tumor This tumor also showed microsatellite instability, and this is the first report of such a defect in gastrinomas. This study implicates chromosome 1 defects, aneuploidy, and perhaps mismatch repair defects as importan features of gastrinomas; deletions involving the MEN1 gene were con firmed, but the rest of the genome was free of large deletions or amplifications.

Authors+Show Affiliations

Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland 20892, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

11034099

Citation

Yu, F, et al. "Survey of Genetic Alterations in Gastrinomas." Cancer Research, vol. 60, no. 19, 2000, pp. 5536-42.
Yu F, Jensen RT, Lubensky IA, et al. Survey of genetic alterations in gastrinomas. Cancer Res. 2000;60(19):5536-42.
Yu, F., Jensen, R. T., Lubensky, I. A., Mahlamaki, E. H., Zheng, Y. L., Herr, A. M., & Ferrin, L. J. (2000). Survey of genetic alterations in gastrinomas. Cancer Research, 60(19), 5536-42.
Yu F, et al. Survey of Genetic Alterations in Gastrinomas. Cancer Res. 2000 Oct 1;60(19):5536-42. PubMed PMID: 11034099.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Survey of genetic alterations in gastrinomas. AU - Yu,F, AU - Jensen,R T, AU - Lubensky,I A, AU - Mahlamaki,E H, AU - Zheng,Y L, AU - Herr,A M, AU - Ferrin,L J, PY - 2000/10/18/pubmed PY - 2001/2/28/medline PY - 2000/10/18/entrez SP - 5536 EP - 42 JF - Cancer research JO - Cancer Res VL - 60 IS - 19 N2 - Gastrinomas are rare gastrin-secreting endocrine tumors that usually arise in the duodenum or pancreas and, if untreated, can cause severe peptic ulcers or metastatic disease. Although most tumors are sporadic they are especially common in patients with multiple endocrine neoplasia type 1 (MEN1), and most studies of these tumors have focused on the role of the MEN1 gene. Although the gene is commonly altered in sporadic tumors, this finding is not universal, and it is highly likely that other genetic defects play a significant role. In the present study, an in-depth analysis of the DNA of eight tumors was carried out in an effort to localize these areas. The experiments consisted of an analysis of 400 microsatellite marker loci distributed evenly throughout the human genome, and the results were confirmed with comparative genomic hybridization. Whereas deletions encompassing the MEN1 gene were seen in two tumors, the most striking result was multiple large rearrangements on chromosome 1 in two of the tumors with hepatic metastases. In several instances, an individual tumor had abnormalities of every informative maker on a given chromosome, presumably as a result of aneuploidy affecting that chromosome. Such defects were only seen in the four large or aggressive tumors, and the total number of chromosomes affected in a tumor ranged from 1 to a high of 13 in a patient who had an unusually aggressive tumor This tumor also showed microsatellite instability, and this is the first report of such a defect in gastrinomas. This study implicates chromosome 1 defects, aneuploidy, and perhaps mismatch repair defects as importan features of gastrinomas; deletions involving the MEN1 gene were con firmed, but the rest of the genome was free of large deletions or amplifications. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/11034099/Survey_of_genetic_alterations_in_gastrinomas_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=11034099 DB - PRIME DP - Unbound Medicine ER -