Comparison of Global DNA Methylation Patterns in Human Melanoma Tissues and Their Derivative Cell Lines

Abstract

DNA methylation is a heritable epigenetic mark that is fundamental to mammalian development. Aberrant DNA methylation is an epigenetic hallmark of cancer cells. Cell lines are a critical in vitro model and very widely used to unravel mechanisms of cancer cell biology. However, limited data are available to assess whether DNA methylation patterns in tissues are retained when cell lines are established. Here, we provide the first genome-scale sequencing-based methylation map of metastatic melanoma tumour tissues and their derivative cell lines. We show that DNA methylation profiles are globally conserved in vitro compared to the tumour tissue of origin. However, we identify sites that are consistently hypermethylated in cell lines compared to their tumour tissue of origin. The genes associated with these common differentially methylated regions are involved in cell metabolism, cell cycle and apoptosis and are also strongly enriched for the H3K27me3 histone mark and PRC2 complex-related genes. Our data indicate that although global methylation patterns are similar between tissues and cell lines, there are site-specific epigenomic differences that could potentially impact gene expression. Our work provides a valuable resource for identifying false positives due to cell culture and for better interpretation of cancer epigenetics studies in the future.

Locus-Specific DNA Methylation Editing in Melanoma Cell Lines Using a CRISPR-Based System

“…Immortalized cell lines are widely used as an experimental model for the fundamental investigation of tumor cell biology. DNA methylation status has been demonstrated to be well conserved between tumor tissue samples and derivative cell lines; therefore, cell lines provide an effective in vitro model for studying epigenetic alterations in cancer cells [ 4 , 20 , 21 ]. Our editing system comprises three main components: a dCas9-SunTag targeting protein; locus-specific guide RNA (gRNA; sgRNA) construct; and an effector construct for manipulating DNA methylation ( Figure 1 ).…”

Multi-omic characterization of ILC and ILC-like cell lines as part of ILC cell line encyclopedia (ICLE) defines new models to study potential biomarkers and explore therapeutic opportunities

“…We found that overall breast cancer cell lines showed more aberrant DNAm (high DMI) than patient tumors (Supplementary Figure S4E,F). Higher DMI in cell lines in part maybe driven by culture condition induced epigenetic changes 86,87 .…”

Genome-wide promoter methylation profiling in a cellular model of melanoma progression reveals markers of malignancy and metastasis that predict melanoma survival

“…In addition, melanoma tissue specimens, a diversity of patient treatment procedures could contribute to the heterogeneous molecular alterations observed in different studies. Moreover, adjacent tissue and lymphocyte infiltrates can influence the results of studies using tissue biopsies [ 11 , 12 ].…”