Back to Search
Start Over
Functional epigenomics approach to identify methylated candidate tumour suppressor genes in renal cell carcinoma.
- Source :
- British Journal of Cancer; 1/29/2008, Vol. 98 Issue 2, p496-501, 6p, 1 Diagram, 1 Chart, 2 Graphs
- Publication Year :
- 2008
-
Abstract
- Promoter region hypermethylation and transcriptional silencing is a frequent cause of tumour suppressor gene (TSG) inactivation in many human cancers. Previously, to identify candidate epigenetically inactivated TSGs in renal cell carcinoma (RCC), we monitored changes in gene expression in four RCC cell lines after treatment with the demethylating agent 5-azacytidine. This enabled us to identify HAI-2/SPINT2 as a novel epigenetically inactivated candidate RCC TSG. To identify further candidate TSGs, we undertook bioinformatic and molecular genetic evaluation of a further 60 genes differentially expressed after demethylation. In addition to HAI-2/SPINT2, four genes (PLAU, CDH1, IGFB3 and MT1G) had previously been shown to undergo promoter methylation in RCC. After bioinformatic prioritisation, expression and/or methylation analysis of RCC cell lines+/-primary tumours was performed for 34 genes. KRT19 and CXCL16 were methylated in RCC cell lines and primary RCC; however, 22 genes were differentially expressed after demethylation but did not show primary tumour-specific methylation (methylated in normal tissue (n=1); methylated only in RCC cell lines (n=9) and not methylated in RCC cell lines (n=12)). Re-expression of CXCL16 reduced growth of an RCC cell line in vitro. In a summary, a functional epigenomic analysis of four RCC cell lines using microarrays representing 11 000 human genes yielded both known and novel candidate TSGs epigenetically inactivated in RCC, suggesting that this is valid strategy for the identification of novel TSGs and biomarkers. [ABSTRACT FROM AUTHOR]
- Subjects :
- METHYLATION
TUMOR suppressor genes
RENAL cell carcinoma
GENE expression
BIOINFORMATICS
CELL lines
CELL receptors
COMPARATIVE studies
CYTOKINES
GENES
GENETIC techniques
KIDNEY tumors
RESEARCH methodology
MEDICAL cooperation
ONCOGENES
RESEARCH
RESEARCH funding
STEM cells
GENOMICS
EVALUATION research
DNA methylation
Subjects
Details
- Language :
- English
- ISSN :
- 00070920
- Volume :
- 98
- Issue :
- 2
- Database :
- Complementary Index
- Journal :
- British Journal of Cancer
- Publication Type :
- Academic Journal
- Accession number :
- 28611084
- Full Text :
- https://doi.org/10.1038/sj.bjc.6604180