Identification of MEN1 gene mutations in sporadic carcinoid tumors of the lung

Larisa V. Debelenko, Elisabeth Brambilla, Sunita K. Agarwal, Jennifer I. Swalwell, Mary B. Kester, Irina A. Lubensky, Zhengping Zhuang, Siradanahalli C. Guru, Pachiappan Manickam, Shodimu Emmanuel Olufemi, Settara C. Chandrasekharappa, Judy S. Crabtree, Young S. Kirn, Christina Heppner, A. Lee Burns, Allen M. Spiegel, Stephen J. Marx, Lance A. Liotta, Francis S. Collins, William D. TravisMichael R. Emmert-Buck

Research output: Contribution to journalArticle

223 Scopus citations

Abstract

Lung carcinoids occur sporadically and rarely in association with multiple endocrine neoplasia type 1 (MEN1). There are no well defined genetic abnormalities known to occur in these tumors. We studied 11 sporadic lung carcinoids for loss of heterozygosity (LOH) at the locus of the MEN1 gene on chromosome 11q13, and for mutations of the MEN1 gene using dideoxy fingerprinting. Additionally, a lung carcinoid from a MEN1 patient was studied. In four of 11 (36%) sporadic tumors, both copies of the MEN1 gene were inactivated. All four tumors showed the presence of a MEN1 gene mutation and loss of the other allele. Observed mutations included a 1 bp insertion, a 1 bp deletion, a 13 bp deletion and a single nucleotide substitution affecting a donor splice site. Each mutation predicts truncation or potentially complete loss of menin. The remaining seven tumors showed neither the presence of a MEN1 gene mutation nor 11q13 LOH. The tumor from the MEN1 patient showed LOH at chromosome 11q13 and a complex germline MEN1 gene mutation. The data implicate the MEN1 gene in the pathogenesis of sporadic lung carcinoids, representing the first defined genetic alteration in these tumors.

Original languageEnglish (US)
Pages (from-to)2285-2290
Number of pages6
JournalHuman molecular genetics
Volume6
Issue number13
DOIs
StatePublished - Dec 1997
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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    Debelenko, L. V., Brambilla, E., Agarwal, S. K., Swalwell, J. I., Kester, M. B., Lubensky, I. A., Zhuang, Z., Guru, S. C., Manickam, P., Olufemi, S. E., Chandrasekharappa, S. C., Crabtree, J. S., Kirn, Y. S., Heppner, C., Burns, A. L., Spiegel, A. M., Marx, S. J., Liotta, L. A., Collins, F. S., ... Emmert-Buck, M. R. (1997). Identification of MEN1 gene mutations in sporadic carcinoid tumors of the lung. Human molecular genetics, 6(13), 2285-2290. https://doi.org/10.1093/hmg/6.13.2285