Project description:MicroRNAs play a vital role in the process of tumorigenesis. To identify and characterize miRNA Expression in renal cell cancer, we performed microarray based screening of miRNA expression profiles in clear cell, papillary type 1 and papillary type 2 renal cell cancer. We selected cases of confirmed clear cell, papillary type 1 and papillary type 2 renal cell carcinoma and generated pairs of tumor and corresponding normal tissue by manual microdissection.
Project description:Papillary renal cell carcinoma type 2 (PRCC2) is known to be very aggressive type of tumor without effictive therapy. Hereditary form of PRCC2 is caused by Fumarate Hydratase (FH) gene mutation that accompanied Hereditary Leiomyomatosis and Renal Cell Carcinoma (HLRCC) disorder. In sporadic form of PRCC2 the mutation of FH gene has not been reported. Both forms of tumors have the similar histopathological characteristics with poor survival prognosis. In this study, we profiled the gene expression of renal tumors and normal tissue from PRCC2 (hereditary and sporadic) patients in order to better understand commonalities and differences in the transcriptional landscape of PRCC2. Microarray gene expression profiling was performed on eight normal kidney tissue samples, five hereditary PRCC2 tumor tissue samples and 19 sporadic PRCC2 tumor tissue samples. Hereditary PRCC2 (HPRCC2) patients were confirmed by DNA sequencing of the FH gene.
Project description:Renal cell carcinoma is the most common neoplasm of the adult kidney. A few subtypes of RCC include papillary RCC (pRCC), chromophobe RCC (chRCC) and the benign oncocytoma tumor. In some cases, distinguishing between the RCC subyptes is difficult. We performed a mircroRNA (miRNA) microarray to determine differential miRNA expression between pRCC, chRCC, and oncocytoma. We performed a miRNA microarray on 10 tumor samples of each papillary renal cell carcinoma (pRCC), chromophobe renal cell carcinoma (chRCC), and oncocytoma.
Project description:Copy number variant (CNV) analysis was performed on renal cell carcinoma (RCC) specimens (chromophobe, clear cell, oncocytoma, papillary type 1, papillary type 2) using high resolution arrays (1.85 million probes). RCC samples exhibited diverse genomic changes within and across tumor types ranging from 106 CNV segments in a clear cell specimen to 2238 CNV segments in a papillary type 2 specimen. Despite the genomic heterogeneity, distinct CNV segments were common within each of 4 tumor classifications: chromophobe (7 segments), clear cell (3 segments), oncocytoma (9 segments), and papillary type 2 (2 segments). Shared segments ranged from a 6.1 Kb deletion among oncocytomas to a 208.3 Kb deletion common to chromophobes. Among common tumor type-specific variations, chromophobe, clear cell and oncocytomas comprised exclusively non-coding DNA. No CNV regions were common to papillary type 1 specimens although there were 12 amplifications and 12 deletions in 5 of 6 samples. Three microRNAs and 12 mRNA genes had M-bM-^IM-% 98% of their coding region contained within CNV regions including multiple gene families (chromophobe: amylase 1A, 1B, 1C; oncocytoma: general transcription factor 2H2, 2B, 2C, 2D). Gene deletions involved in histone modification and chromatin remodeling affected individual subtypes (clear cell: SFMBT, SETD2; papillary type 2: BAZ1A) as well as the collective RCC group (KDM4C). The genomic amplifications/deletions identified in each renal tumor type represent potential diagnostic and/or prognostic biomarkers. Tissue samples were obtained from the University of Pittsburgh Health Sciences Tissue Bank (HSTB) using an honest broker system and according to IRB approved protocol #970480. Samples were acquired as surgical specimens, flash-frozen in a 1.8 ml cryotube (NalgeNunc, Inc., Rochester, NY) followed by immediate storage at -80C. Each tumor sample (n=27) was classified into one of 5 renal cancer subtypes (chromophobe: n=5, clear cell: n=5, oncocytoma: n=5, papillary type 1: n=6, papillary type 2: n=6) by consensus evaluation of correlative hematoxylin and eosin stained slides performed independently by 3 anatomical pathologists. The three pathologists also confirmed the absence of pathological features in adjacent normal renal samples (n=9) and this normal reference group was expanded by inclusion of 14 normal thyroid samples and 8 normal lung specimens. DNA from each of these specimens was analyzed using genotyping microarrays (SNP 6.0, Affymetrix, Sunnyvale, CA).
Project description:Comprehensive transcriptome studies of cancers often rely on corresponding normal tissue samples to serve as a transcriptional reference. In this study we performed in-depth analyses of normal kidney tissue transcriptomes from TCGA and demonstrate that the histological variability in cellularity, inherent in the kidney architecture, lead to considerable transcriptional differences between samples. This should be considered when comparing expression profiles of normal and cancerous kidney tissues. We exploited these differences to define renal cell-specific gene signatures and used these as framework to analyze renal cell carcinoma (RCC) ontogeny. Chromophobe RCCs express FOXI1-driven genes that define collecting duct intercalated cells whereas HNF-regulated genes, specific for proximal tubule cells, are an integral part of clear cell and papillary RCC transcriptomes. These networks may be used as framework for understanding the interplay between genomic changes in RCC subtypes and the lineage-defining regulatory machinery of their non-neoplastic counterparts.
Project description:The proteome of clinical tissue samples diagnosed with clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma (pRCC) were evaluated analyzed along with the dataset identifier PXD022018 to establish a potential discriminative biomarker panel of proteins for these tumors subtypes.