PMID- 10738303
OWN - NLM
STAT- MEDLINE
DCOM- 20000516
LR  - 20191025
IS  - 1045-2257 (Print)
IS  - 1045-2257 (Linking)
VI  - 28
IP  - 1
DP  - 2000 May
TI  - MEN1 gene mutation analysis of high-grade neuroendocrine lung carcinoma.
PG  - 58-65
AB  - 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.
FAU - Debelenko, L V
AU  - Debelenko LV
AD  - Laboratory of Pathology, National Cancer Institute, NIH, Bethesda, Maryland, USA.
FAU - Swalwell, J I
AU  - Swalwell JI
FAU - Kelley, M J
AU  - Kelley MJ
FAU - Brambilla, E
AU  - Brambilla E
FAU - Manickam, P
AU  - Manickam P
FAU - Baibakov, G
AU  - Baibakov G
FAU - Agarwal, S K
AU  - Agarwal SK
FAU - Spiegel, A M
AU  - Spiegel AM
FAU - Marx, S J
AU  - Marx SJ
FAU - Chandrasekharappa, S C
AU  - Chandrasekharappa SC
FAU - Collins, F S
AU  - Collins FS
FAU - Travis, W D
AU  - Travis WD
FAU - Emmert-Buck, M R
AU  - Emmert-Buck MR
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - United States
TA  - Genes Chromosomes Cancer
JT  - Genes, chromosomes & cancer
JID - 9007329
RN  - 0 (DNA, Neoplasm)
RN  - 0 (MEN1 protein, human)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Proto-Oncogene Proteins)
SB  - IM
MH  - Carcinoma, Large Cell/genetics
MH  - Carcinoma, Neuroendocrine/*genetics
MH  - Carcinoma, Small Cell/genetics
MH  - Chromosomes, Human, Pair 11/genetics
MH  - DNA Mutational Analysis/methods
MH  - DNA, Neoplasm/*analysis
MH  - Humans
MH  - Loss of Heterozygosity/genetics
MH  - Lung Neoplasms/*genetics
MH  - Multiple Endocrine Neoplasia Type 1/genetics
MH  - Neoplasm Proteins/*genetics
MH  - *Proto-Oncogene Proteins
MH  - Tumor Cells, Cultured
EDAT- 2000/03/30 09:00
MHDA- 2000/05/20 09:00
CRDT- 2000/03/30 09:00
PHST- 2000/03/30 09:00 [pubmed]
PHST- 2000/05/20 09:00 [medline]
PHST- 2000/03/30 09:00 [entrez]
AID - 10.1002/(SICI)1098-2264(200005)28:1<58::AID-GCC7>3.0.CO;2-2 [pii]
AID - 10.1002/(sici)1098-2264(200005)28:1<58::aid-gcc7>3.0.co;2-2 [doi]
PST - ppublish
SO  - Genes Chromosomes Cancer. 2000 May;28(1):58-65. doi: 
      10.1002/(sici)1098-2264(200005)28:1<58::aid-gcc7>3.0.co;2-2.