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

Zhengping Zhuang, Alexander O. Vortmeyer, Svetlana Pack, Steve Huang, Thu A. Pham, Chaoyu Wang, Won Sang Park, Sunita K. Agarwal, Larisa V. Debelenko, Mary Beth Kester, Siradanahalli C. Guru, Pachiappan Manickam, Shodimu Emmanuel Olufemi, Fang Yu, Christina Heppner, Judy S. Crabtree, Monica C. Skarulis, David J. Venzon, Michael R. Emmert-Buck, Allen M. SpiegelSettara C. Chandrasekharappa, Francis S. Collins, A. Lee Burns, Stephen J. Marx, Robert T. Jensen, Lance A. Liotta, Irina A. Lubensky

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255 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4682-4686
Number of pages5
JournalCancer Research
Volume57
Issue number21
StatePublished - Nov 1 1997
Externally publishedYes

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Zhuang, Z., Vortmeyer, A. O., Pack, S., Huang, S., Pham, T. A., Wang, C., Park, W. S., Agarwal, S. K., Debelenko, L. V., Kester, M. B., Guru, S. C., Manickam, P., Olufemi, S. E., Yu, F., Heppner, C., Crabtree, J. S., Skarulis, M. C., Venzon, D. J., Emmert-Buck, M. R., ... Lubensky, I. A. (1997). Somatic mutations of the MEN1 tumor suppressor gene in sporadic gastrinomas and insulinomas. Cancer Research, 57(21), 4682-4686.