Project description:Blood-borne miRNA signatures have recently been reported for various tumor diseases. Here, we compared the miRNA signature in Wilms tumor patients prior to and after preoperative chemotherapy according to the SIOP protocol 2001. We did not find a significant difference between the miRNA signatures of both groups. However, both Wilms tumor patients prior to and after chemotherapy showed a miRNA signature different from that of healthy controls. The signature of Wilms tumor patients prior to chemotherapy showed an accuracy of 97.5% and of patients after chemotherapy an accuracy of 97.0%, each as compared to healthy controls. Our results provide evidence for a blood-borne Wilms tumor miRNA signature largely independent of four weeks preoperative chemotherapy treatment.
Project description:Abstract: Background: MiRNA signatures in human sera have been reported for various tumor diseases. Here we generated miRNA profiles analyzing 1205 mature miRNA transcripts of serum samples of Wilms tumor patients, taken prior and after chemotherapy according to SIOP protocol 2001. Using a feature subset selection filter approach we identified a minimal number of miRNAs with a maximum contribution for the classification between treated and untreated patients and between patients and controls. Results: Analyzing 1205 mature miRNAs, we separated controls and Wilms tumor patients prior chemotherapy with an accuracy of 0.81. We obtained a similar accuracy (0.82) for the separation between controls and sera of Wilms tumor patients after preoperative chemotherapy. We identified 23 miRNAs that were differentially expressed in both comparisons. Subset selection improved the overall classification accuracy between controls and Wilms tumor patients prior and after chemotherapy to 0.94 and 0.91, respectively. Subset selection also allowed separating between Wilms tumor patients prior and after chemotherapy with an accuracy of 0.98. Conclusion: Our analysis identified serum based miRNA signatures that allowed separating between controls, untreated Wilms tumor patients, and Wilms tumor patients after chemotherapy with high accuracy for each of these comparisons.
Project description:This SuperSeries is composed of the following subset Series: GSE17342: The role of miRNA in Wilms' tumorigenesis GSE28397: Copy number alteration in Wilms' tumor with custom-designed miRNA probes GSE28400: MIR-204 target gene Refer to individual Series
Project description:Blood-borne miRNA signatures have recently been reported for various tumor diseases. Here, we compared the miRNA signature in Wilms tumor patients prior to and after preoperative chemotherapy according to the SIOP protocol 2001. We did not find a significant difference between the miRNA signatures of both groups. However, both Wilms tumor patients prior to and after chemotherapy showed a miRNA signature different from that of healthy controls. The signature of Wilms tumor patients prior to chemotherapy showed an accuracy of 97.5% and of patients after chemotherapy an accuracy of 97.0%, each as compared to healthy controls. Our results provide evidence for a blood-borne Wilms tumor miRNA signature largely independent of four weeks preoperative chemotherapy treatment. This project analyzes peripheral blood profiles of Wilms tumor patients and controls in order to detect specific profiles. n=19 normal controls and n=23 Wilms tumor patients were screened for the complete miRNA repertoire. Please note that each miRNA has been measured in seven replicates and the median of the replica has been computed.
Project description:The aim of the study was to identify differentially expressed miRNAs in different Wilms tumor subtypes. Comparison of miRNA expression profiles in Wilms tumor of different subtypes (total n=62) compared to normal kidney tissue (n=4)
Project description:The aim of this study is to discover loss of specific miRNA loci in Wilms' tumors using array CGH. Custom arrays were designed based on the Agilent 2x105K Human Whole Genome Genomic microarray with Agilent’s eArray program (https://earray.chem.agilent.com/earray/), with additional probes that cover all miRNA regions (200 bps before, within and after each miRNA from miRBase v13, with each probe in triplicates to enhance the reliability). All custom-designed probes were designed in UCSC hg18. Probes from Agilent’s database were lifted-over from hg19 to hg18 (LiftOver tool: http://genome.ucsc.edu). The Agilent 2x105K custom-design whole genome microarray was used to analyze genomic alterations in Wilms' tumor samples compared to normal human genomic DNA (Promega p/n G1523).
Project description:The aim of the study was to identify differentially expressed mRNAs in different Wilms tumor subtypes and correlate them to miRNA expression profiles of the same tumor samples.
Project description:Wilms tumor (nephroblastoma) is a pediatric kidney tumor that arises from renal progenitor cells. Since the blastemal type is associated with adverse prognosis, we characterized such Wilms tumors by exome and transcriptome analysis. We detected novel, recurrent somatic mutations affecting the SIX1/2 – SALL1 pathway implicated in kidney development, the DROSHA/DGCR8 microprocessor genes as well as alterations in MYCN and TP53, the latter being strongly associated with dismal outcome. The DROSHA mutations impair the RNase III domains, while DGCR8 exhibits stereotypic E518K mutations in the RNA binding domain - both may skew miRNA representation. SIX1 and SIX2 mutations affect a single hotspot (Q177R) in the homeodomain indicative of a dominant effect. In larger cohorts, these mutations cluster in blastemal and chemotherapy-induced regressive tumors that likely derive from blastemal cells and these are characterized by generally higher SIX1/2 expression. These findings broaden the spectrum of human cancer genes and may open new avenues for stratification and therapeutic leads for Wilms tumors. 53 Wilms tumor samples were selected for RNA extraction and hybridization on Affymetrix Affymetrix Human Genome U133 Plus 2.0 Arrays.