For example, promoter methylation has been shown to have an important role in regulation of the IGF2 gene [37–39] and loci at 11p13 and 11p15 in Wilms tumors [16]. Improper splicing, a mechanism that contributes to dysregulation of the Wilms tumor suppressor gene WT1, might also contribute to the observed downregulation of SOSTDC1 in kidney cancer [37]. Although our limited sample size does not allow us to buy Tariquidar definitively refute the hypothesis that LOH is the primary regulator of SOSTDC1 in pediatric and adult renal

tumors, we suggest that other modes of regulation must also be considered. Future experiments that investigate alternative regulatory mechanisms such as epigenetic silencing of SOSTDC1 may uncover more pertinent contributors to the reduced SOSTDC1 protein levels observed in renal cancer. Conclusions AZD8931 chemical structure This study investigates the role of SOSTDC1, a candidate renal tumor suppressor gene, in adult and pediatric renal tumors. We observed within an analysis of the Oncomine database that SOSTDC1 is expressed in normal renal tissue and that its expression is decreased in adult and pediatric renal cancer. When adult renal cell carcinoma samples were

investigated for LOH within SOSTDC1, we found that LOH was present in five of 36 adult renal carcinoma samples and four GW3965 cell line of 25 Wilms tumors. This led us to investigate the possibility that SOSTDC1 LOH correlates with reduced protein levels or altered signaling. Our analyses did not reveal any consistent correlations between SOSTDC1 LOH and either SOSTDC1 protein levels or signaling. These findings point to the possibility that SOSTDC1 downregulation within adult and pediatric renal tumors may be attributable to a mechanism other than LOH, such as epigenetic silencing. Acknowledgements This project was supported in part by grant NIH R21CA119181 (ST). KC acknowledges support from the T32CA079448 training grant from the National Cancer Institute. The authors also acknowledge generous support mafosfamide for this work from the Ben Mynatt

family. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. Electronic supplementary material Additional file 1: Map of the SOSTDC1 locus. Arrows indicate the relative positions of designed primer pairs to potential regions of interest within the SOSTDC1 gene. The sizes of the known and putative exons are noted above the map; intron sizes are indicated below. The gene translation start codon is in exon 3 and the stop codon is in exon 5. All known coding sequences are contained within exons 3 and 5 (denoted by black boxes). Putative exons 1, 2, and 4 are highlighted by gray boxes. Data summarized from the Genome Browser hosted at UCSC. (TIFF 39 KB) Additional file 2: Primers for direct sequencing of SOSTDC1. Target exon, forward (F) and reverse (R) primer sequences, and amplicon sizes are shown.