BioProject

Previously, we have reported that genomic loss of 14q occurs more frequently in high grade clear cell renal cell carcinomas (ccRCCs) than low grade ones and shows a significant impact on the expression levels of genes located on this region, suggesting that the genes located on the region and downregulated by the loss may be involved in the malignant transformation of ccRCCs. More...

Previously, we have reported that genomic loss of 14q occurs more frequently in high grade clear cell renal cell carcinomas (ccRCCs) than low grade ones and shows a significant impact on the expression levels of genes located on this region, suggesting that the genes located on the region and downregulated by the loss may be involved in the malignant transformation of ccRCCs. Here, among the genes located on the minimal common region of 14q loss, we found that 6 were significantly downregulated in high grade ccRCCs due to copy number loss. Using the data set from The Cancer Genome Atlas (TCGA) Research Network, downregulation of one out of the 6 genes, WDR20, was significantly associated with poorer prognosis for the patients with ccRCC, suggesting that downregulation of WDR20 may be involved in the malignant transformation of ccRCC. In functional assays, exogeneous WDR20 significantly inhibited growth and induced apoptosis in RCC cell lines. Interestingly, the phosphorylation levels of ERK and AKT, which reportedly contribute to the malignant phenotype of RCC cells, were clearly reduced by the exogeneous expression of WDR20. Thus, our data suggest that downregulation of WDR20 due to 14q loss may be involved in the malignant transformation of ccRCCs in part through the activation of ERK and AKT pathways. Overall design: Downregulated expression levels of genes in minimal common region due to 14q loss. Expression levels of 6 genes were determined by microarray analysis and compared between normal kidney tissues (normal, n=16), low grade (low, n=16) and high grade (high, n=16) ccRCCs. The expression level (log2) normalized by the median expression level for the 16 normal samples. Less...