CpG methylation profiling in lung cancer cell lines, tumors and non-tumors.

摘要

Cell lines are widely used for studying DNA methylation in cancer. Their main applications are in the development of biomarkers, in pharmacological studies and for studying the effect of demethylating agents and for studying the effect of methylation on biological pathways. Studies have compared the methylation status in cell lines to primary tumors in various cancers. Conflicting conclusions have been made as to whether cell lines represent the methylation observed in tumors.;In this study I have used the Illumina Goldengate assay to compare the methylation status of 1506 CpG loci (807 genes) in adenocarcinoma cell lines, adeno and squamous frozen tumors and non-tumor lung samples. Hierarchical clustering was performed to study the methylation profile in each of these samples and to study the degree of similarity between adenocarcinoma cell lines and frozen tumors. Further performing parametric tests, I observed that cell lines do exhibit cancer-specific hypermethylation, closely resembling that of frozen tumors. On performing Wilcoxon rank sum test on tumors and cell lines at all loci and applying additional filters on loci that were significantly different, I observed that 10 genes were significantly hypermethylated and 5 genes were significantly hypomethylated in cell lines as compared to adeno tumors at more than one locus of the gene. Hence, cell lines may show differences in degree of methylation for few genes. Based on the assumption that this cell line specific hypomethylation might be associated with expression of genes and cell line-specific hypermethylation to gene silencing, I tried to deduce their effect on biological pathways. I conclude that cell lines would be appropriate models for studying hypermethylation and for development of biomarkers but might not be appropriate models for studying WNT pathway.