Comparison of Global DNA Methylation Patterns in Human Melanoma Tissues and Their Derivative Cell Lines
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 avail...
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MDPI AG
2021-04-01
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Series: | Cancers |
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Online Access: | https://www.mdpi.com/2072-6694/13/9/2123 |
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author | Euan J. Rodger Suzan N. Almomani Jackie L. Ludgate Peter A. Stockwell Bruce C. Baguley Michael R. Eccles Aniruddha Chatterjee |
author_facet | Euan J. Rodger Suzan N. Almomani Jackie L. Ludgate Peter A. Stockwell Bruce C. Baguley Michael R. Eccles Aniruddha Chatterjee |
author_sort | Euan J. Rodger |
collection | DOAJ |
description | 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. |
first_indexed | 2024-03-10T11:53:14Z |
format | Article |
id | doaj.art-9aef6f398a9a44e1bdb278c9438e2fac |
institution | Directory Open Access Journal |
issn | 2072-6694 |
language | English |
last_indexed | 2024-03-10T11:53:14Z |
publishDate | 2021-04-01 |
publisher | MDPI AG |
record_format | Article |
series | Cancers |
spelling | doaj.art-9aef6f398a9a44e1bdb278c9438e2fac2023-11-21T17:32:56ZengMDPI AGCancers2072-66942021-04-01139212310.3390/cancers13092123Comparison of Global DNA Methylation Patterns in Human Melanoma Tissues and Their Derivative Cell LinesEuan J. Rodger0Suzan N. Almomani1Jackie L. Ludgate2Peter A. Stockwell3Bruce C. Baguley4Michael R. Eccles5Aniruddha Chatterjee6Department of Pathology, Otago Medical School—Dunedin Campus, University of Otago, Dunedin 9054, New ZealandDepartment of Pathology, Otago Medical School—Dunedin Campus, University of Otago, Dunedin 9054, New ZealandDepartment of Pathology, Otago Medical School—Dunedin Campus, University of Otago, Dunedin 9054, New ZealandDepartment of Pathology, Otago Medical School—Dunedin Campus, University of Otago, Dunedin 9054, New ZealandMaurice Wilkins Centre for Molecular Biodiscovery, Auckland 1010, New ZealandDepartment of Pathology, Otago Medical School—Dunedin Campus, University of Otago, Dunedin 9054, New ZealandDepartment of Pathology, Otago Medical School—Dunedin Campus, University of Otago, Dunedin 9054, New ZealandDNA 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.https://www.mdpi.com/2072-6694/13/9/2123methylationcell cultureepigeneticscancerin vitro |
spellingShingle | Euan J. Rodger Suzan N. Almomani Jackie L. Ludgate Peter A. Stockwell Bruce C. Baguley Michael R. Eccles Aniruddha Chatterjee Comparison of Global DNA Methylation Patterns in Human Melanoma Tissues and Their Derivative Cell Lines Cancers methylation cell culture epigenetics cancer in vitro |
title | Comparison of Global DNA Methylation Patterns in Human Melanoma Tissues and Their Derivative Cell Lines |
title_full | Comparison of Global DNA Methylation Patterns in Human Melanoma Tissues and Their Derivative Cell Lines |
title_fullStr | Comparison of Global DNA Methylation Patterns in Human Melanoma Tissues and Their Derivative Cell Lines |
title_full_unstemmed | Comparison of Global DNA Methylation Patterns in Human Melanoma Tissues and Their Derivative Cell Lines |
title_short | Comparison of Global DNA Methylation Patterns in Human Melanoma Tissues and Their Derivative Cell Lines |
title_sort | comparison of global dna methylation patterns in human melanoma tissues and their derivative cell lines |
topic | methylation cell culture epigenetics cancer in vitro |
url | https://www.mdpi.com/2072-6694/13/9/2123 |
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