Promoter methylation of the TSLC1 gene in advanced lung tumors and various cancer cell lines.

Abstract

We previously identified TSLC1, a tumor suppressor gene in human nonsmall cell lung cancer (NSCLC). TSLC1 belongs to immunoglobulin superfamily molecules and is involved in cell adhesion. Loss of TSLC1 expression was strongly correlated with the promoter hypermethylation in several NSCLC cell lines. Here, we examined the methylation status of the TSLC1 gene promoter in 48 primary NSCLC tumors by bisulfite SSCP in combination with bisulfite sequencing. Six CpG sites around the promoter regions were significantly methylated in 21 of 48 primary NSCLC tumors (44%). Promoter methylation was more likely to be observed in relatively advanced tumors with TNM classification of pT2, pT3 or pT4 (19 of 33, 58%) than in those with pT1 (2 of 15, 13%), suggesting that alteration of TSLC1 would be involved in the progression of human NSCLC. Loss of TSLC1 expression was also observed in 20 of 46 (43%) human cancer cell lines, including those from esophageal (3 of 3), gastric (8 of 9), ovarian (2 of 5), endometrial (2 of 2), breast (1 of 3), colorectal (2 of 8) and small cell lung cancers (2 of 10). Combined analysis of promoter methylation and the allelic state in these cell lines indicated that the TSLC1 gene was often silenced not only by mono-allelic methylation associated with loss of the other allele but also through bi-allelic methylation. These results suggest that alteration of TSLC1 would be involved in advanced NSCLC as well as in many other human cancers.