MicroRNA expression data from human renal cell cancer subtypes
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ABSTRACT: 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:MicroRNAs are small RNA molecules of about 21-25 nucleotides that regulate gene expression via posttranscriptional inhibition of protein synthesis. They play a vital role in the process of tumorigenesis. To identify and characterize the diagnostic potential of miRNAs in prostate cancer, a leading cause of tumor mortality, we performed microarray based screening of miRNA expression profiles. We selected 20 cases of moderately differentiated prostate cancer and generated pairs of tumor and corresponding normal tissue by microdissection
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.
Project description:Papillary renal cell carcinomas (pRCC) are the second most common form of renal carcinoma, after clear cell Renal carcinoma (ccRCC). PRCC account for 10 to 15% of RCC and gather a heterogeneous population with no specific systemic treatment. Pathological classification by Elbe divides pRCC population in two morphologically different subtypes. Type 1 consists of predominantly basophilic cells, whereas type 2 contains mostly eosinophilic cells. Type 1 architecture corresponds with a single line of cells along the papillary axis, whereas type 2 generally exhibits several cell strata on the axis. Furthermore, type 2 cells demonstrate more aggressive characteristics, such as the presence of nucleoli and increased nuclear size. The papillary cores often contain edema fluid, foamy macrophages, and psammoma bodies. Further clinical reports identified that type I tumors are more likely to present as numerous, bilateral , indolent, low grade pRCC, whereas type II are associated with higher grade and poor prognosis related to metastatic evolution.
Project description:Papillary renal cell carcinomas (pRCC) are the second most common form of renal carcinoma, after clear cell Renal carcinoma (ccRCC). PRCC account for 10 to 15% of RCC and gather a heterogeneous population with no specific systemic treatment. Pathological classification by Elbe divides pRCC population in two morphologically different subtypes. Type 1 consists of predominantly basophilic cells, whereas type 2 contains mostly eosinophilic cells. Type 1 architecture corresponds with a single line of cells along the papillary axis, whereas type 2 generally exhibits several cell strata on the axis. Furthermore, type 2 cells demonstrate more aggressive characteristics, such as the presence of nucleoli and increased nuclear size. The papillary cores often contain edema fluid, foamy macrophages, and psammoma bodies. Further clinical reports identified that type I tumors are more likely to present as numerous, bilateral , indolent, low grade pRCC, whereas type II are associated with higher grade and poor prognosis related to metastatic evolution. The goal of this study wad to characterize each sample in order to get an idea of the genomic profile in pRCC type 2 (pRCCII).
Project description:Clear cell papillary renal cell carcinoma (CCPRCC) is a low-grade renal neoplasm with morphological characteristics mimicking both clear cell renal cell carcinoma (CCRCC) and papillary renal cell carcinoma (PRCC). However, despite some overlapping features, their morphological, immunohistochemical, and molecular profiles are distinct. To better understand the biology of this tumor, we analyze the miRNA expression profiles of a set of CCPRCC by microarrays.
Project description:Long non-coding RNA (lncRNA) play an important role in several biological processes including some renal diseases. Nevertheless, little is known on lncRNAs that are expressed in healthy kidney and involved in renal cell homeostasis and development and even less is known about lncRNA involved in the maintenance of human adult renal stem/progenitor cells (ARPCs). ARPCs have been shown to be very important for renal homeostasis and repair processes thanks to their self-renewal and differentiative ability as well as their capacity to secrete different reparative factors depending on the type of damage. Through a whole genome transcriptome screening, we found that the HOTAIR lncRNA is highly expressed in renal progenitors and potentially involved cell cycle and senescence biological processes. We then generated HOTAIR knock-out ARPC lines by CRISPR/Cas9 genome editing and showed that this lncRNA limits the apoptotic process of ARPCs and sustains their proliferative capacity, thus resulting responsible of their self-renewal properties. In addition, we found that the knockout of HOTAIR led to the ARPC senescence and to a significant decrease of the CD133 stem cell marker expression that is an inverse marker of ARPC senescence and can regulate renal tubular repair after the damage. Moreover, we found that ARPCs expressed high levels of the α-Klotho anti-aging protein and especially 2.6 fold higher levels compared to that secreted by RPTECs. The HOTAIR knockout in ARPCs leads to lower α-Klotho levels, comparable to that of RPTECs. Finnally we showed that HOTAIR induces epigenetic silencing of the cell cycle inhibitor p15 through the trimethylation of the histone H3K27. Altogether, these results shed new light on these important renal cells and may support the future development of precision therapies for kidney diseases.
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 ≥ 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.
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:Intra-tumour heterogeneity (ITH) foster tumour adaptation and hamper the efficiency of personalised medicine approaches. We investigated the extent of ITH within individual clear cell renal cell carcinomas (ccRCC) by multi-region sampling and copy number analysis. We analyzed 63 tumour regions and 8 normal samples from eight clear cell renal cell carcinomas using Affymetrix SNP6 arrays. All individual tumours were subjected to multi-region sampling and copy-number analysis using Affymetrix SNP6 arrays.