Genome-wide methylation analysis identifies genes silenced in non-seminoma cell lines
Silencing of genes by DNA methylation is a common phenomenon in many types of cancer. However, the genome wide effect of DNA methylation on gene expression has been analysed in relatively few cancers. Germ cell tumours (GCTs) are a complex group of malignancies. They are unique in developing from a...
| Main Authors: | , , , , , , , , , , , , |
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Nature Publishing Group
2016
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| Online Access: | https://eprints.nottingham.ac.uk/32049/ |
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| author | Noor, Dzul Azri Mohamed Jeyapalan, Jennie N. Alhazmi, Safiah Carr, Matthew Squibb, Benjamin Wallace, Claire Tan, Christopher Cusack, Martin Hughes, Jaime Reader, Tom Shipley, Janet Sheer, Denise Scotting, Paul J. |
| author_facet | Noor, Dzul Azri Mohamed Jeyapalan, Jennie N. Alhazmi, Safiah Carr, Matthew Squibb, Benjamin Wallace, Claire Tan, Christopher Cusack, Martin Hughes, Jaime Reader, Tom Shipley, Janet Sheer, Denise Scotting, Paul J. |
| author_sort | Noor, Dzul Azri Mohamed |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | Silencing of genes by DNA methylation is a common phenomenon in many types of cancer. However, the genome wide effect of DNA methylation on gene expression has been analysed in relatively few cancers. Germ cell tumours (GCTs) are a complex group of malignancies. They are unique in developing from a pluripotent progenitor cell. Previous analyses have suggested that non-seminomas exhibit much higher levels of DNA methylation than seminomas. The genomic targets that are methylated, the extent to which this results in gene silencing and the identity of the silenced genes most likely to play a role in the tumours’ biology have not yet been established. In this study, genome-wide methylation and expression analysis of GCT cell lines was combined with gene expression data from primary tumours to address this question. Genome methylation was analysed using the Illumina infinium HumanMethylome450 bead chip system and gene expression was analysed using Affymetrix GeneChip Human Genome U133 Plus 2.0 arrays. Regulation by methylation was confirmed by demethylation using 5-aza-2-deoxycytidine and reverse transcription–quantitative PCR. Large differences in the level of methylation of the CpG islands of individual genes between tumour cell lines correlated well with differential gene expression. Treatment of non-seminoma cells with 5-aza-2-deoxycytidine verified that methylation of all genes tested played a role in their silencing in yolk sac tumour cells and many of these genes were also differentially expressed in primary tumours. Genes silenced by methylation in the various GCT cell lines were identified. Several pluripotency-associated genes were identified as a major functional group of silenced genes. |
| first_indexed | 2025-11-14T19:14:24Z |
| format | Article |
| id | nottingham-32049 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:14:24Z |
| publishDate | 2016 |
| publisher | Nature Publishing Group |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-320492020-05-04T17:32:22Z https://eprints.nottingham.ac.uk/32049/ Genome-wide methylation analysis identifies genes silenced in non-seminoma cell lines Noor, Dzul Azri Mohamed Jeyapalan, Jennie N. Alhazmi, Safiah Carr, Matthew Squibb, Benjamin Wallace, Claire Tan, Christopher Cusack, Martin Hughes, Jaime Reader, Tom Shipley, Janet Sheer, Denise Scotting, Paul J. Silencing of genes by DNA methylation is a common phenomenon in many types of cancer. However, the genome wide effect of DNA methylation on gene expression has been analysed in relatively few cancers. Germ cell tumours (GCTs) are a complex group of malignancies. They are unique in developing from a pluripotent progenitor cell. Previous analyses have suggested that non-seminomas exhibit much higher levels of DNA methylation than seminomas. The genomic targets that are methylated, the extent to which this results in gene silencing and the identity of the silenced genes most likely to play a role in the tumours’ biology have not yet been established. In this study, genome-wide methylation and expression analysis of GCT cell lines was combined with gene expression data from primary tumours to address this question. Genome methylation was analysed using the Illumina infinium HumanMethylome450 bead chip system and gene expression was analysed using Affymetrix GeneChip Human Genome U133 Plus 2.0 arrays. Regulation by methylation was confirmed by demethylation using 5-aza-2-deoxycytidine and reverse transcription–quantitative PCR. Large differences in the level of methylation of the CpG islands of individual genes between tumour cell lines correlated well with differential gene expression. Treatment of non-seminoma cells with 5-aza-2-deoxycytidine verified that methylation of all genes tested played a role in their silencing in yolk sac tumour cells and many of these genes were also differentially expressed in primary tumours. Genes silenced by methylation in the various GCT cell lines were identified. Several pluripotency-associated genes were identified as a major functional group of silenced genes. Nature Publishing Group 2016-01-13 Article PeerReviewed Noor, Dzul Azri Mohamed, Jeyapalan, Jennie N., Alhazmi, Safiah, Carr, Matthew, Squibb, Benjamin, Wallace, Claire, Tan, Christopher, Cusack, Martin, Hughes, Jaime, Reader, Tom, Shipley, Janet, Sheer, Denise and Scotting, Paul J. (2016) Genome-wide methylation analysis identifies genes silenced in non-seminoma cell lines. Genomic Medicine, 1 (15009). pp. 1-13. ISSN 2056-7944 cancer genomics DNA methylation gene expression onco genesis http://www.nature.com/articles/npjgenmed20159 doi:10.1038/npjgenmed.2015.9 doi:10.1038/npjgenmed.2015.9 |
| spellingShingle | cancer genomics DNA methylation gene expression onco genesis Noor, Dzul Azri Mohamed Jeyapalan, Jennie N. Alhazmi, Safiah Carr, Matthew Squibb, Benjamin Wallace, Claire Tan, Christopher Cusack, Martin Hughes, Jaime Reader, Tom Shipley, Janet Sheer, Denise Scotting, Paul J. Genome-wide methylation analysis identifies genes silenced in non-seminoma cell lines |
| title | Genome-wide methylation analysis identifies genes silenced in non-seminoma cell lines |
| title_full | Genome-wide methylation analysis identifies genes silenced in non-seminoma cell lines |
| title_fullStr | Genome-wide methylation analysis identifies genes silenced in non-seminoma cell lines |
| title_full_unstemmed | Genome-wide methylation analysis identifies genes silenced in non-seminoma cell lines |
| title_short | Genome-wide methylation analysis identifies genes silenced in non-seminoma cell lines |
| title_sort | genome-wide methylation analysis identifies genes silenced in non-seminoma cell lines |
| topic | cancer genomics DNA methylation gene expression onco genesis |
| url | https://eprints.nottingham.ac.uk/32049/ https://eprints.nottingham.ac.uk/32049/ https://eprints.nottingham.ac.uk/32049/ |