tumor and nontumorous lung tissue specimens from NSCLC patients. MATERIALS AND METHODS Tissue Samples and DNA Extraction. Peripheral lung tumors and nontu

The aim of this study was to examine the association between DNA hypermethylation and dlinicopathological features of non-small cell lung cancers (NSCLCs). The DNA methylation status at the DJ7SS 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 fre quently in poorly than in well-differentiated tumors, especially in adeno carcinomas, and correlated significantly with the differentiation grade (P = 0.01). DNA hypermethylation at the D17S5 locus correlated signif icantly with the loss of heterozygosity at this locus in tumors (P = 0.01). The incidence ofDNA hypermethylatlon was significantly higher in smok era 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 DJ7SS locus may play a role in the development of NSCLCS in cigarette smokers.