TY - JOUR
T1 - Identification of candidate tumour suppressor genes frequently methylated in renal cell carcinoma
AU - Morris, Mark
AU - Ricketts, Christopher
AU - Gentle, Dean
AU - Abdulrahman, M
AU - Clarke, N
AU - Brown, M
AU - Kishida, T
AU - Yao, M
AU - Latif, Farida
AU - Maher, Eamonn
PY - 2010/4/1
Y1 - 2010/4/1
N2 - Promoter region hyermethylation 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 induced by 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 11 renal cell carcinoma (RCC) cell lines. Twenty-eight genes were then selected for analysis of promoter methylation status in cell lines and primary RCC. Eight genes (BNC1, PDLIM4, RPRM, CST6, SFRP1, GREM1, COL14A1 and COL15A1) showed frequent (>30% of RCC tested) tumour-specific promoter region methylation. Hypermethylation was associated with transcriptional silencing. Re-expression of BNC1, CST6, RPRM and SFRP1 suppressed the growth of RCC cell lines and RNA interference knock-down of BNC1, SFRP1 and COL14A1 increased the growth of RCC cell lines. Methylation of BNC1 or COL14A1 was associated with a poorer prognosis independent of tumour size, stage or grade. The identification of these epigenetically inactivated candidate RCC TSGs can provide insights into renal tumourigenesis and a basis for developing novel therapies and biomarkers for prognosis and detection. Oncogene (2010) 29, 2104-2117; doi: 10.1038/onc.2009.493; published online 15 February 2010
AB - Promoter region hyermethylation 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 induced by 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 11 renal cell carcinoma (RCC) cell lines. Twenty-eight genes were then selected for analysis of promoter methylation status in cell lines and primary RCC. Eight genes (BNC1, PDLIM4, RPRM, CST6, SFRP1, GREM1, COL14A1 and COL15A1) showed frequent (>30% of RCC tested) tumour-specific promoter region methylation. Hypermethylation was associated with transcriptional silencing. Re-expression of BNC1, CST6, RPRM and SFRP1 suppressed the growth of RCC cell lines and RNA interference knock-down of BNC1, SFRP1 and COL14A1 increased the growth of RCC cell lines. Methylation of BNC1 or COL14A1 was associated with a poorer prognosis independent of tumour size, stage or grade. The identification of these epigenetically inactivated candidate RCC TSGs can provide insights into renal tumourigenesis and a basis for developing novel therapies and biomarkers for prognosis and detection. Oncogene (2010) 29, 2104-2117; doi: 10.1038/onc.2009.493; published online 15 February 2010
KW - methylation
KW - renal cell carcinoma
KW - epigenetics
U2 - 10.1038/onc.2009.493
DO - 10.1038/onc.2009.493
M3 - Article
C2 - 20154727
VL - 29
SP - 2104
EP - 2117
JO - Oncogene
JF - Oncogene
IS - 14
ER -
