Elsevier

Neoplasia

Volume 2, Issue 4, July–August 2000, Pages 300-305
Neoplasia

Mutation and Expression of the DCC Gene in Human Lung Cancer1

https://doi.org/10.1038/sj.neo.7900094Get rights and content
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open access

Abstract

Chromosome 18q is frequently deleted in lung cancers, a common region of 18q deletions was mapped to chromosome 18g21. Since the DCC candidate tumor suppressor gene has been mapped in this region, mutation and expression of the DCC gene were examined in 46 lung cancer cell lines, consisting of 14 small cell lung carcinomas (SCLCs) and 32 non-small cell lung carcinomas (NSCLCs), to elucidate the pathogenetic significance of DCC alterations in human lung carcinogenesis. A heterozygous missense mutation was detected in a NSCLC cell line, Ma26, while homozygous deletion was not detected in any of the cell lines. The DCC gene was expressed in 11 (24%) of the 46 cell lines, the incidence of DCC expression was significantly higher in SCLCs (7/14, 50%) than in NSCLCs (4/32, 13%) (P = .01, Fisher's exact test). Therefore, genetic alterations of DCC are infrequent; however, the levels of DCC expression vary among lung cancer cells, in particular, between SCLCs and NSCLCs. The present result does not implicate DCC as a specific mutational target of 18q deletions in human lung cancer; however, it suggests that DCC is a potential target of inactivation by genetic defects including intron or promoter mutations and/or epigenetic alterations. The present result also suggests that DCC expression is associated with some properties of SCLCs, such as a neuroendocrine (NE) feature.

Keywords

DCC
lung cancer
chromosome 18
tumor suppressor gene
mutation

Abbreviations

SCLC
small cell lung carcinoma
NSCLC
non-small cell lung carcinoma
SSCP
single-strand conformation polymorphism
SNP
single nucleotide polymorphism
LOH
loss of heterozygosity
At
allelic imbalance
RT-PCR
reverse transcription polymerase chain reaction
NE
neuroendocrine

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1

This work was supported, in part, by a Grant-in-Aid from the Ministry of Health and Welfare for the second term Comprehensive 10-Year Strategy for Cancer Control, a Grant-in-Aid from the Ministry of Health and Welfare for Research on Human Genome and Gene Therapy, Grants-in-Aid from the Ministry of Health and Welfare and from the Ministry of Education, Science, Sports and Culture of Japan.