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MEN1 gene mutation analysis of high-grade neuroendocrine lung carcinoma.

Publication ,  Journal Article
Debelenko, LV; Swalwell, JI; Kelley, MJ; Brambilla, E; Manickam, P; Baibakov, G; Agarwal, SK; Spiegel, AM; Marx, SJ; Chandrasekharappa, SC ...
Published in: Genes Chromosomes Cancer
May 2000

Neuroendocrine tumors of the lung consist of a spectrum of neoplasms, including typical carcinoids, atypical carcinoids, large-cell neuroendocrine carcinomas (LCNEC), and small-cell lung carcinomas (SCLC). We previously reported frequent inactivation of the gene responsible for multiple endocrine neoplasia type 1 (MEN1) in both typical and atypical carcinoid tumors. In the present study, we extend the analysis of human NE lung tumors to include 9 primary SCLCs, 36 SCLC cell lines, and 13 primary LCNECs for MEN1 gene inactivation. In SCLC, loss of heterozygosity (LOH) at the MEN1 gene on chromosome band 11q13 was detected in one primary tumor and two cell lines. The coding sequence and splice junctions of the MEN1 gene were screened for mutations in all 44 tumors and cell lines, and no mutations were detected. Northern blot analysis of 13 SCLC cell lines showed the MEN1 transcript to be present and of normal size. In LCNECs, a somatic frameshift in the MEN1 gene (1226delC) was found in one of 13 tumors, representing the first mutation observed outside the spectrum of neoplasms associated with MEN1. Interestingly, neither a deletion nor a mutation was detected in the other allele, and wild-type mRNA sequence was expressed in the tumor, suggesting that the MEN1 gene was not inactivated by a conventional two-hit mechanism. The data support the hypothesis that SCLC and lung carcinoids develop via distinct molecular pathways; however, further investigation is necessary to determine the significance of the MEN1 gene mutation observed in a single case of LCNEC. Published 2000 Wiley-Liss, Inc.

Duke Scholars

Published In

Genes Chromosomes Cancer

DOI

ISSN

1045-2257

Publication Date

May 2000

Volume

28

Issue

1

Start / End Page

58 / 65

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Proto-Oncogene Proteins
  • Oncology & Carcinogenesis
  • Neoplasm Proteins
  • Multiple Endocrine Neoplasia Type 1
  • Lung Neoplasms
  • Loss of Heterozygosity
  • Humans
  • DNA, Neoplasm
  • DNA Mutational Analysis
 

Citation

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Debelenko, L. V., Swalwell, J. I., Kelley, M. J., Brambilla, E., Manickam, P., Baibakov, G., … Emmert-Buck, M. R. (2000). MEN1 gene mutation analysis of high-grade neuroendocrine lung carcinoma. Genes Chromosomes Cancer, 28(1), 58–65. https://doi.org/10.1002/(sici)1098-2264(200005)28:1<58::aid-gcc7>3.0.co;2-2
Debelenko, L. V., J. I. Swalwell, M. J. Kelley, E. Brambilla, P. Manickam, G. Baibakov, S. K. Agarwal, et al. “MEN1 gene mutation analysis of high-grade neuroendocrine lung carcinoma.Genes Chromosomes Cancer 28, no. 1 (May 2000): 58–65. https://doi.org/10.1002/(sici)1098-2264(200005)28:1<58::aid-gcc7>3.0.co;2-2.
Debelenko LV, Swalwell JI, Kelley MJ, Brambilla E, Manickam P, Baibakov G, et al. MEN1 gene mutation analysis of high-grade neuroendocrine lung carcinoma. Genes Chromosomes Cancer. 2000 May;28(1):58–65.
Debelenko, L. V., et al. “MEN1 gene mutation analysis of high-grade neuroendocrine lung carcinoma.Genes Chromosomes Cancer, vol. 28, no. 1, May 2000, pp. 58–65. Pubmed, doi:10.1002/(sici)1098-2264(200005)28:1<58::aid-gcc7>3.0.co;2-2.
Debelenko LV, Swalwell JI, Kelley MJ, Brambilla E, Manickam P, Baibakov G, Agarwal SK, Spiegel AM, Marx SJ, Chandrasekharappa SC, Collins FS, Travis WD, Emmert-Buck MR. MEN1 gene mutation analysis of high-grade neuroendocrine lung carcinoma. Genes Chromosomes Cancer. 2000 May;28(1):58–65.
Journal cover image

Published In

Genes Chromosomes Cancer

DOI

ISSN

1045-2257

Publication Date

May 2000

Volume

28

Issue

1

Start / End Page

58 / 65

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Proto-Oncogene Proteins
  • Oncology & Carcinogenesis
  • Neoplasm Proteins
  • Multiple Endocrine Neoplasia Type 1
  • Lung Neoplasms
  • Loss of Heterozygosity
  • Humans
  • DNA, Neoplasm
  • DNA Mutational Analysis