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Somatic mutations of the MEN1 tumor suppressor gene in sporadic gastrinomas and insulinomas.

Abstract
Gastrinomas and insulinomas are frequent in multiple endocrine neoplasia type 1 (MEN1). The MEN1 tumor suppressor gene was recently identified. To elucidate the etiological role of the MEN1 gene in sporadic enteropancreatic endocrine tumorigenesis, we analyzed tumors (28 gastrinomas and 12 insulinomas) from 40 patients for MEN1 gene mutations and allelic deletions. One copy of the MEN1 gene was found to be deleted in 25 of 27 (93%) sporadic gastrinomas and in 6 of 12 (50%) sporadic insulinomas. MEN1 gene mutations were identified in 9 of 27 (33%) sporadic gastrinomas and 2 of 12 (17%) insulinomas and were not seen in corresponding germ-line DNA sequence. A specific MEN1 mutation was detected in one gastrinoma and in the corresponding germ-line DNA of a patient who had no family history of MEN1. Somatic MEN1 gene mutations and deletions play a critical role in the tumorigenesis of sporadic gastrinomas and may also contribute to the development of a subgroup of insulinomas.
AuthorsZ Zhuang, A O Vortmeyer, S Pack, S Huang, T A Pham, C Wang, W S Park, S K Agarwal, L V Debelenko, M Kester, S C Guru, P Manickam, S E Olufemi, F Yu, C Heppner, J S Crabtree, M C Skarulis, D J Venzon, M R Emmert-Buck, A M Spiegel, S C Chandrasekharappa, F S Collins, A L Burns, S J Marx, I A Lubensky
JournalCancer research (Cancer Res) Vol. 57 Issue 21 Pg. 4682-6 (Nov 01 1997) ISSN: 0008-5472 [Print] United States
PMID9354421 (Publication Type: Journal Article)
Chemical References
  • DNA, Neoplasm
Topics
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • DNA Mutational Analysis
  • DNA, Neoplasm (genetics)
  • Female
  • Gastrinoma (genetics)
  • Gene Deletion
  • Genes, Tumor Suppressor (genetics)
  • Germ-Line Mutation
  • Humans
  • In Situ Hybridization, Fluorescence
  • Insulinoma (genetics)
  • Jejunal Neoplasms (genetics)
  • Male
  • Middle Aged
  • Multiple Endocrine Neoplasia Type 1 (genetics)
  • Mutation (genetics)
  • Pancreatic Neoplasms (genetics)

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