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MEN1 gene mutation analysis of high‐grade neuroendocrine lung carcinoma
Author(s) -
Debelenko Larisa V.,
Swalwell Jennifer I.,
Kelley Michael J.,
Brambilla Elisabeth,
Manickam Pachiappan,
Baibakov Galina,
Agarwal Sunita K.,
Spiegel Allen M.,
Marx Stephen J.,
Chandrasekharappa Settara C.,
Collins Francis S.,
Travis William D.,
EmmertBuck Michael R.
Publication year - 2000
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/(sici)1098-2264(200005)28:1<58::aid-gcc7>3.0.co;2-2
Subject(s) - men1 , loss of heterozygosity , biology , frameshift mutation , cancer research , multiple endocrine neoplasia , neuroendocrine tumors , mutation , germline mutation , gene , gene mutation , microbiology and biotechnology , genetics , allele , endocrinology
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 MEN 1 gene inactivation. In SCLC, loss of heterozygosity (LOH) at the MEN 1 gene on chromosome band 11q13 was detected in one primary tumor and two cell lines. The coding sequence and splice junctions of the MEN 1 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 MEN 1 transcript to be present and of normal size. In LCNECs, a somatic frameshift in the MEN 1 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 MEN 1 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 MEN 1 gene mutation observed in a single case of LCNEC. Genes Chromosomes Cancer 28:58–65, 2000. Published 2000 Wiley‐Liss, Inc.