Genomic Heterogeneity and the Small Renal Mass
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PROVIDER: EGAC00001000875 | EGA |
REPOSITORIES: EGA
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Project description:Purpose: Tumor heterogeneity may represent a barrier to preoperative genomic characterization by needle biopsy in clear cell renal cell carcinoma (ccRCC). The extent of heterogeneity in small renal tumors remains unknown. Therefore, we set out to evaluate heterogeneity in resected large and small renal tumors.Experimental Design: We conducted a study from 2013 to 2016 that evaluated 47 consecutive ccRCC tumors resected during radical or partial nephrectomy. Cases were designated as small (<4 cm) and large (>7 cm) tumors. Each tumor had three regions sampled. Copy-number variation (CNV) was assessed and gene expression analysis was performed to characterize the clear-cell A and B (ccA/ccB) profile and the cell-cycle progression (CCP) score. Genomic heterogeneity between three regions was evaluated using CNV subclonal events, regional expression profiles, and correlation between gene expression.Results: Twenty-three small and 24 large tumors were analyzed. Total CNVs and subclonal CNVs events were less frequent in small tumors (P < 0.001). Significant gene expression heterogeneity was observed for both CCP scores and ccA/ccB classifications. Larger tumors had more variance in CCP scores (P = 0.026). The distribution of ccA/ccB differed between small and large tumors with mixed ccA/ccB tumors occurring more frequently in the larger tumors (P = 0.024). Analysis of five mixed tumors (with both ccA/ccB regions) demonstrated the more aggressive ccB phenotype had greater CNV events (P = 0.014).Conclusions: Small renal tumors have much less genomic complexity and fewer subclonal events. Pretreatment genomic characterization with single-needle biopsy in small tumors may be useful to assess biologic potential and may influence therapy. Clin Cancer Res; 24(17); 4137-44. ©2018 AACR.
| S-EPMC6125159 | biostudies-literature
Project description:Tumor heterogeneity is believed to represent a barrier to pre-operative genomic characterization in kidney cancer. Previous studies of heterogeneity in clear cell renal cell carcinoma (ccRCC) evaluated only large and metastatic tumors. In small renal tumors in which multiple biopsies are not feasible, the extent of heterogeneity remains unknown. In this study, we evaluated how the extent of genomic heterogeneity in small and large ccRCC. A total of 23 small (<4cm ) and 24 large (>7cm ) ccRCC had 3 regions sampled for evaluation of copy number, clear-cell A/clear-cell B (ccA/ccB) classification, and cell cycle progression (CCP) score. Small tumors have less genomic complexity and significantly fewer subclonal events. Pre-treatment genomic characterization based on a single biopsy in small ccRCC can provide insight into biologic potential to make clinical decisions.
| EGAS00001002919 | EGA
Project description:Joint Addiction, Aging, and Mental Health Data Access Committee General Research Use Datasets
| PRJNA934662 | ENA
Project description:Joint Addiction, Aging, and Mental Health Data Access Committee General Research Use Datasets
| PRJNA934661 | ENA
Project description:Translocation renal cell carcinoma (tRCC) is a rare subtype of kidney cancer involving the TFEB/TFE3 genes. We aimed to investigate the genomic and epigenetic features of this entity.Cytogenomic analysis was conducted with 250K single-nucleotide polymorphism microarrays on 16 tumor specimens and four cell lines. LINE-1 methylation, a surrogate marker of DNA methylation, was conducted on 27 cases using pyrosequencing.tRCC showed cytogenomic heterogeneity, with 31.2% and 18.7% of cases presenting similarities with clear-cell and papillary RCC profiles, respectively. The most common alteration was a 17q gain in seven tumors (44%), followed by a 9p loss in six cases (37%). Less frequent were losses of 3p and 17p in five cases (31%) each. Patients with 17q gain were older (P=0.0006), displayed more genetic alterations (P<0.003), and had a worse outcome (P=0.002) than patients without it. Analysis comparing gene-expression profiling of a subset of tumors bearing 17q gain and those without suggest large-scale dosage effects and TP53 haploinsufficiency without any somatic TP53 mutation identified. Cell line-based cytogenetic studies revealed that 17q gain can be related to isochromosome 17 and/or to multiple translocations occurring around 17q breakpoints. Finally, LINE-1 methylation was lower in tRCC tumors from adults compared with tumors from young patients (71.1% vs. 76.7%; P=0.02).Our results reveal genomic heterogeneity of tRCC with similarities to other renal tumor subtypes and raise important questions about the role of TFEB/TFE3 translocations and other chromosomal imbalances in tRCC biology.
| S-EPMC3882157 | biostudies-literature
Project description:Joint Addiction, Aging, and Mental Health Data Access Committee General Research Use Datasets (GSR restricted) Collection
| PRJNA1018664 | ENA
Project description:Joint Addiction, Aging, and Mental Health Data Access Committee General Research Use Datasets (GSR restricted) Collection
| PRJNA1018662 | ENA
Project description:Data Access Committee EGAC00001002236
| EGAC00001002236 | EGA
Project description:Azacitidine (AZA) and decitabine (DAC) are cytidine azanucleoside analogs with clinical activity in myelodysplastic syndromes (MDS) and potential activity in solid tumors. To better understand the mechanism of action of these drugs, we examined the effects of AZA and DAC in a panel of non-small cell lung cancer (NSCLC) cell lines. Of 5 NSCLC lines tested in a cell viability assay, all were sensitive to AZA (EC50 of 1.8M-bM-^@M-^S10.5 M-BM-5M), while only H1299 cells were equally sensitive to DAC (EC50 of 5.1 M-BM-5M). In the relatively DAC-insensitive cell line A549, both AZA and DAC caused DNA methyltransferase I depletion and DNA hypomethylation; however, only AZA significantly induced markers of DNA damage and apoptosis, suggesting that mechanisms in addition to, or other than, DNA hypomethylation are important for AZA-induced cell death. Cell cycle analysis indicated that AZA induced an accumulation of cells in sub-G1 phase, whereas DAC mainly caused an increase of cells in G2/M. Gene expression analysis of AZA- and DAC-treated cells revealed strikingly different profiles, with many genes distinctly regulated by each drug. In summary, while both AZA and DAC caused DNA hypomethylation, distinct effects were demonstrated on regulation of gene expression, cell cycle, DNA damage, and apoptosis. A549 and H1299 cells were treated with a dose range (0.3M-bM-^@M-^S3.0 M-NM-<M) of AZA or DAC for 48 hours, and effects on gene expression were assessed by microarray analysis.
2011-05-05 | E-GEOD-29077 | biostudies-arrayexpress