Project description:VHL loss is the most common genetic alteration event in ccRCC, but its effect on epigenetic landscape has not been elucidated previously. We describe the genome-wide cis-regulatory landscapes of VHL-deficient ccRCC tumors by comparing the epigenetic changes in terms of histone modifications (H3K27ac, H3K4me1, H3K4me3) with the transcriptomics profiles in 10 pairs of normal kidney and ccRCC tissues.
Project description:Renal cell carcinoma (RCC) is the most common neoplasm of the adult kidney. Currently, there are no biomarkers for the diagnostic, prognostic, or predictive applications in RCC. MicroRNAs (miRNAs) are short non protein-coding RNAs that negatively regulate gene expression and have been shown to be involved in cancer. We analyzed a total of 70 matched pairs of clear cell RCC (ccRCC) and normal kidney tissues from the same patients by microarray analysis and validated our results by quantitative real time PCR. We identified 166 miRNAs significantly dysregulated in ccRCC. MiR-122, miR-155 and miR-210 had the highest fold changes of overexpression while miR-200c, miR-335, and miR-218 were the most downregulated. We performed extensive bioinformatics analysis including a combinatorial analysis of previously reported miRNAs dysregulated in RCC and extensive target prediction analysis. Many miRNAs were predicted to target a number of genes involved in RCC pathogenesis. Our results showed that miRNA dysregulation in RCC can be attributed in part, to chromosomal aberrations, the co-regulation of miRNA clusters, and co-expression with host genes. We also correlated miRNA expression with clinical characteristics and found miR-155 expression was correlated with ccRCC tumor size. In conclusion, our analysis showed that a number of miRNAs are dysregulated in ccRCC and may contribute to kidney cancer pathogenesis by targeting more than one key molecule. We identified mechanisms that may contribute to miRNA dysregulation in ccRCC. Dysregulated miRNAs represent potential biomarkers for kidney cancer. We preformed a miRNA microarray on 20 pairs of matched primary clear cell renal cell carcinoma (ccRCC) and normal kidney tissue from the same patient (St. Michael's Hospital, Toronto, Canada). One matched pair was used per array for a total of 20 arrays. Microarray results were validated by quantitative real time PCR using an independent set of 50 matched pairs of ccRCC and normal kidney tissue from the same patient.
Project description:Genome wide DNA methylation profiling of clear cell renal cell carcinoma (ccRCC) tissue versus matched normal kidney tissue. The Illumina Infinium 450k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 450,000 CpGs in tumor and adjacent normal kidney tissue samples from ccRCC patients. Samples included 46 paired fresh frozen ccRCC tumor and adjacent normal kidney tissues.
Project description:Genome wide DNA methylation profiling of clear cell renal cell carcinoma (ccRCC) tissue versus matched normal kidney tissue. The Illumina Infinium 450k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 450,000 CpGs in tumor and adjacent normal kidney tissue samples from ccRCC patients. Samples included 46 paired fresh frozen ccRCC tumor and adjacent normal kidney tissues. Bisulphite converted DNA from the 92 samples were hybridised to the Illumina Infinium 450 Human Methylation Beadchip v1.2
Project description:We aimed to assess differences in miRNA expression profiles in transcriptomic molecular subtypes of ccRCC (Beuselinck et al, Clinical Cancer Research 2015) and to correlate miRNAs with overal survival since diagnosis of ccRCC. Sequencing was done for 129 primary ccRCC (formalin-fixed paraffin-embedded surgical resection specimens, previously untreated) and 16 normal kidney specimens. Normal kidney was obtained from the nephrectomy specimens at time of ccRCC removal, in tissue blocks containing only normal kidney (so nót the normal kidney immediately adjacent to ccRCC). The samples were sequenced in 2 major batches (2014 and 2017).
Project description:Genome wide DNA methylation profiling of normal kidney (n=36), nephrogenic rest (n=22) and Wilms tumour (n=37) was performed using the Illumina 450k array. Two papers were composed after analysis of this data (1) describes comparative analysis of 22 matched normal kidney-Wilms tumour pairs which identified biomarker differentially methylated regions (DMRs) that could be detected in patient blood; (2) describes comparative analysis of 20 matched trios which identified changes in methylation associated with progression from the precursor lesion towards tumourigenesis.
Project description:Currently there is a lack of effective therapies which result in long-term durable response for patients presenting with advanced and metastatic clear cell renal cell carcinoma (ccRCC). This is due in part to a lack of molecular factors which can be targeted pharmacologically. In order to identify novel tumor-specific targets, we performed high throughput gene array analysis screening numerous patient ccRCC tumor tissues across all stages of disease, and compared their gene expression levels to matched normal kidney. Our results identify a number of genes which demonstrate tumor-specific overexpression, and may present as novel targets for therapy. Patient tissue samples were sorted into disease stages based on pathology reports. RNA was extracted from flash frozen patient tumor and normal samples. Gene array analysis was performed, and resulting expression levels were compared between normal and tumor samples.
Project description:Formalin fixed paraffin embedded (FFPE) primary-recurrent Glioblastoma (pGBM-rGBM) matched patient samples and normal tissue adjacent to tumor (NAT) were analyzed by shotgun DDA proteomics. The proteomic profiles of pGBM-rGBM pairs revealed differentially expressed proteins in rGBM samples, which in future could be used for potential therapeutic interventions.
Project description:Renal cell carcinoma (RCC) is the most common and lethal cancer of the adult kidney. Its incidence is increasing and outcomes remain poor. Accurate discrimination of RCC patients with poor prognosis was very important for the appropriate and effective patient management. ccRCC originated from dysregulation of different gene expression. To screen novel prognosis markers, a dysregulated mRNA expression profile was identified by microarray in some pairs of different stages ccRCC.