| Summary: | <p>Abstract</p> <p>Background</p> <p>Deletions within the short arm of chromosome 7 are observed in approximately 25% of adult and 10% of Wilms pediatric renal tumors. Within Wilms tumors, the region of interest has been delineated to a 2-Mb minimal region that includes ten known genes. Two of these ten candidate genes, <it>SOSTDC1 </it>and <it>MEOX2</it>, are particularly relevant to tumor development and maintenance. This finding, coupled with evidence that SOSTDC1 is frequently downregulated in adult renal cancer and regulates both Wingless-Int (Wnt)- and bone morphogenetic protein (BMP)-induced signaling, points to a role for SOSTDC1 as a potential tumor suppressor.</p> <p>Methods</p> <p>To investigate this hypothesis, we interrogated the Oncomine database to examine the SOSTDC1 levels in adult renal clear cell tumors and pediatric Wilms tumors. We then performed single nucleotide polymorphism (SNP) and sequencing analyses of <it>SOSTDC1 </it>in 25 pediatric and 36 adult renal tumors. Immunohistochemical staining of patient samples was utilized to examine the impact of <it>SOSTDC1 </it>genetic aberrations on SOSTDC1 protein levels and signaling.</p> <p>Results</p> <p>Within the Oncomine database, we found that SOSTDC1 levels were reduced in adult renal clear cell tumors and pediatric Wilms tumors. Through SNP and sequencing analyses of 25 Wilms tumors, we identified four with loss of heterozygosity (LOH) at 7p and three that affected <it>SOSTDC1</it>. Of 36 adult renal cancers, we found five with LOH at 7p, two of which affected <it>SOSTDC1</it>. Immunohistochemical analysis of SOSTDC1 protein levels within these tumors did not reveal a relationship between these instances of <it>SOSTDC1 </it>LOH and SOSTDC1 protein levels. Moreover, we could not discern any impact of these genetic alterations on Wnt signaling as measured by altered beta-catenin levels or localization.</p> <p>Conclusions</p> <p>This study shows that genetic aberrations near <it>SOSTDC1 </it>are not uncommon in renal cancer, and occur in adult as well as pediatric renal tumors. These observations of <it>SOSTDC1 </it>LOH, however, did not correspond with changes in SOSTDC1 protein levels or signaling regulation. Although our conclusions are limited by sample size, we suggest that an alternative mechanism such as epigenetic silencing of <it>SOSTDC1 </it>may be a key contributor to the reduced SOSTDC1 mRNA and protein levels observed in renal cancer.</p>
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