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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.

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Authors

Dzul Azri Mohamed Noor

Jennie N. Jeyapalan

Safiah Alhazmi

Matthew Carr

Benjamin Squibb

Claire Wallace

Christopher Tan

Martin Cusack

Jaime Hughes

TOM READER TOM.READER@NOTTINGHAM.AC.UK
Associate Professor

Janet Shipley

Denise Sheer

Paul J. Scotting



Abstract

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.

Citation

Noor, D. A. M., Jeyapalan, J. N., Alhazmi, S., Carr, M., Squibb, B., Wallace, C., …Scotting, P. J. (2016). Genome-wide methylation analysis identifies genes silenced in non-seminoma cell lines. npj Genomic Medicine, 1(15009), https://doi.org/10.1038/npjgenmed.2015.9

Journal Article Type Article
Publication Date Jan 13, 2016
Deposit Date Mar 2, 2016
Publicly Available Date Mar 2, 2016
Journal Genomic Medicine
Electronic ISSN 2056-7944
Publisher Nature Publishing Group
Peer Reviewed Peer Reviewed
Volume 1
Issue 15009
DOI https://doi.org/10.1038/npjgenmed.2015.9
Keywords cancer genomics, DNA methylation, gene expression, onco genesis
Public URL https://nottingham-repository.worktribe.com/output/772873
Publisher URL http://www.nature.com/articles/npjgenmed20159

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