Tissue specific epigenetic silencing of the distinct tumor suppressor genes in lung cancer

Abstract

The role of aberrant methylation of the cytosine-guanine dinucleotide islands in the promoter region of tumor suppressor genes in lung cancer development is increasingly recognized. DNAs extracted from cancer tissue biopsies of 40 patients with lung cancer were used. Methylated sites of tumor suppressor geneswere examined by bisulfate treatment and methylation-specific PCR method. Strip Assay was used to access the promoter profiles of cytosine-guanine dinucleotide islands. Some of the tumor specimens evaluated showed fully inactive methylated pattern profiles for the tumor suppressor genes that were studied and some showed partially inactive methylated patterns. In lung cancers, the prevalence of SFRP2, p16, DAPK1, HIC1, MGMT promoter methylation status were 11/40(27.5), 8/40(20), 30/40(75), 16/40(40%) and 10/40(25%), respectively. DAPK1 gene inactivation was seen in all (5/5, 100%) the adenocarcinoma type of tumors and was fully hypermethylated in 13/19 squamous cell type (68.4%), 6/9 SCLC (66.7%), and 4/7 malign epithelial (57.1%) tumors. Our results confirm the importance of methylation in the molecular pathogenesis of lung cancer with the majority of tumors having one or more tumor suppressor genes islands methylated for some tumor suppressor genes promoters. Key words: Lung carcinoma, tumor suppressor genes, epigenetic alterations.