A30
Functional epigenomics identifies candidate tumour suppressor genes frequently methylated in renal cell carcinoma
Mark Morris1, Dean Gentle1, Christopher Ricketts1, Noel Clarke2, Michael Brown2, Takeshi Kishida3, Masahiro Yao3, Farida Latif1, Eamonn Maher1
1Cancer Research UK Renal Molecular Oncology Group, University of Birmingham, Birmingham, UK, 2Paterson Institute for Cancer Research, University of Manchester, Manchester, UK, 3Yokohama City University School of Medicine, Yokohama, Japan
Promoter region hypermethylation and transcriptional silencing is a frequent cause of tumour suppressor gene (TSG) inactivation in many types of human cancers. Functional epigenetic studies, in which gene expression is investigated after treatment with demethylating agents, may identify novel genes with tumour-specific methylation. We used high-density gene expression microarrays in a functional epigenetic study of 12 renal cell carcinoma (RCC) cell lines. After bioinformatic prioritisation, 30 genes were analysed for promoter methylation in cell lines and primary RCC. Seven genes (BNC1, RIL, REPRIMO, CST6, SFRP1, COL14a and COL15a) demonstrated frequent (>30% of RCC tested) tumour-specific promoter region methylation. Hypermethylation was associated with transcriptional silencing and re-expression of BNC1, REPRIMO, CST6 and SFRP1 suppressed the growth of RCC cell lines. BNC1 methylation status was significantly associated with prognosis (after allowing for stage and grade). The identification of epigenetically inactivated candidate RCC tumour suppressor genes will provide insights into tumour development in the kidney and provides a basis for developing novel therapies and biomarkers for prognosis and detection.
