DNA hypermethylation at the D17S5 locus in non-small cell lung cancers: its association with smoking history.
The aim of this study was to examine the association between DNA hypermethylation and clinicopathological features of non-small cell lung cancers (NSCLCs). The DNA methylation status at the D17S5 loci, at which a candidate tumor suppressor gene, HIC-1 (hypermethylated in cancer), was identified, of 51 paired tumor and nontumorous lung tissue specimens from NSCLC patients was examined by Southern blot analysis, using a methylation-sensitive restriction enzyme. DNA hypermethylation at this locus was found in 17 (33%) tumors and 16 (31%) nontumorous lung tissues. DNA in hypermethylation at this locus occurred more frequently in poorly than in well-differentiated tumors, especially in adenocarcinomas, and correlated significantly with the differentiation grade (P = 0.01). DNA hypermethylation at the D17S5 locus correlated significantly with the loss of heterozygosity at this locus in tumors (P = 0.01). The incidence of DNA hypermethylation was significantly higher in smokers than those who had never smoked in both tumors and nontumorous lung tissues (P = 0.03 and P = 0.01, respectively). These results suggest that DNA hypermethylation at the D17S5 locus may play a role in the development of NSCLCs in cigarette smokers.
Eguchi
K
K
Pathology Division, National Cancer Center Research Institute, Tokyo, Japan.
Kanai
Y
Y
Kobayashi
K
K
Hirohashi
S
S
D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D019175:DNA Methylation; D005260:Female; D017353:Gene Deletion; D006801:Humans; D008168:Lung / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012907:Smoking / Q000378:metabolism*