Development of a DNA methylation-based diagnostic signature to distinguish benign oncocytoma from renal cell carcinoma
Ontology highlight
ABSTRACT: We profiled DNA methylation in fresh-frozen oncocytoma and chRCC tumors and tumor-adjacent adjacent normal tissue to identify a signature of differentially methylated CpG sites that robustly distinguish oncocytoma from chRCC. DNA methylation profiles were generated for renal oncocytomas (n=12), primary kidney chromophobes (chRCC) (n=8) and primary kidney clear cell carcinomas (ccRCC) (n=2). Also profiled were three oncocytic neoplasms of unclear pathological diagnosis, including two masses described as hybrid oncocytic/chromophobe type (n=2), and one mass described as hybrid oncocytic renal neoplasm. Also profiled were histologically normal adjacent kidney parenchyma tissue (NKP) from a subset of these patients, including NKP from oncocytoma (n=7), chRCC (n=5), ccRCC (n=1), hybrid oncocytic/chromophobe type (n=1), and hybrid oncocytic renal neoplasm (n=1) bearing kidneys (combined n=15 NKP).
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: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.
Project description:[original title] Genomic expression and single-nucleotide polymorphism profiling discriminates chromophobe renal cell carcinoma and oncocytoma. Background : Chromophobe renal cell carcinoma (chRCC) and renal oncocytoma are two distinct but closely related entities with strong morphologic and genetic similarities. While chRCC is a malignant tumor, oncocytoma is usually regarded as a benign entity. The overlapping characteristics are best explained by a common cellular origin, and the biologic differences between chRCC and oncocytoma are therefore of considerable interest in terms of carcinogenesis, diagnosis and clinical management. Previous studies have been relatively limited in terms of examining the differences between oncocytoma and chromophobe RCC. Methods : Gene expression profiling using the Affymetrix HGU133Plus2 platform was applied on chRCC (n=15) and oncocytoma specimens (n=15). Supervised analysis was applied to identify a discriminatory gene signature, as well as differentially expressed genes. Immunohistochemical validation was performed in an independent set of tumors. Results : A novel 14 probe-set signature was developed to classify the tumors internally with 93% accuracy, and this was successfully validated on an external data-set with 94% accuracy. Parafibromin, aquaporin 6, and synaptogyrin 3 were novel immunohistochemical markers effectively discriminating the two pathologic entities. Conclusion : Gene expression profiles and pathway analysis effectively distinguish chRCC from oncocytoma. We have generated a novel transcript predictor that is able to discriminate between the two entities accurately, and which has been validated both in an internal and an independent data-set, implying generalizability. We have identified a series of immunohistochemical markers that are clinically useful in discriminating chRCC and oncocytoma. 30 mRNA profiling samples (15 chromophobe RCC, 15 oncocytoma)
Project description:[original title] Genomic expression and single-nucleotide polymorphism profiling discriminates chromophobe renal cell carcinoma and oncocytoma. Background : Chromophobe renal cell carcinoma (chRCC) and renal oncocytoma are two distinct but closely related entities with strong morphologic and genetic similarities. While chRCC is a malignant tumor, oncocytoma is usually regarded as a benign entity. The overlapping characteristics are best explained by a common cellular origin, and the biologic differences between chRCC and oncocytoma are therefore of considerable interest in terms of carcinogenesis, diagnosis and clinical management. Previous studies have been relatively limited in terms of examining the differences between oncocytoma and chromophobe RCC. Methods : Gene expression profiling using the Affymetrix HGU133Plus2 platform was applied on chRCC (n=15) and oncocytoma specimens (n=15). Supervised analysis was applied to identify a discriminatory gene signature, as well as differentially expressed genes. Immunohistochemical validation was performed in an independent set of tumors. Results : A novel 14 probe-set signature was developed to classify the tumors internally with 93% accuracy, and this was successfully validated on an external data-set with 94% accuracy. Parafibromin, aquaporin 6, and synaptogyrin 3 were novel immunohistochemical markers effectively discriminating the two pathologic entities. Conclusion : Gene expression profiles and pathway analysis effectively distinguish chRCC from oncocytoma. We have generated a novel transcript predictor that is able to discriminate between the two entities accurately, and which has been validated both in an internal and an independent data-set, implying generalizability. We have identified a series of immunohistochemical markers that are clinically useful in discriminating chRCC and oncocytoma.
Project description:Gene expression profiles, high-throughput SNP genotyping, and pathway analysis effectively distinguish chRCC from oncocytoma. We have generated a novel transcript predictor that is able to discriminate between the two entities accurately, and which has been validated both in an internal and an independent data-set, implying generalizability. A cytogenetic alteration, loss of chromosome 1p, common to renal oncocytoma and chRCC has been identified, providing the opportunities for identifying novel tumor suppressor genes and we have identified a series of immunohistochemical markers that are clinically useful in discriminating chRCC and oncocytoma. Oncocytoma and Chromophobe RCC samples - SNP chip analysis
Project description:Gene expression profiles, high-throughput SNP genotyping, and pathway analysis effectively distinguish chRCC from oncocytoma. We have generated a novel transcript predictor that is able to discriminate between the two entities accurately, and which has been validated both in an internal and an independent data-set, implying generalizability. A cytogenetic alteration, loss of chromosome 1p, common to renal oncocytoma and chRCC has been identified, providing the opportunities for identifying novel tumor suppressor genes and we have identified a series of immunohistochemical markers that are clinically useful in discriminating chRCC and oncocytoma.
Project description:A new method for proteomic studies of OCT-embedded samples based on ultrasound energy is proposed. The cleaning of OCT from mouse kidney embedded tissues were evaluated through the aid of ultrasound energy, with two different frequencies. Simultaneously, vortex agitation was used as control. The optimized method obtained was then applied in human tumor kidney biopsies including chromophobe renal cell carcinomas (chRCC) and renal oncocytomas (RO).
Project description:LC-MS/MS based proteomics study of chromophobe renal cell carcinomas versus the adjacent healthy kidney tissues, nine patients included. The chromophobe renal cell carcinoma cells (UOK276) under different conditions were also analyzed.
Project description:In this study, we investigated CNAs of 4 tumor samples from 2 patients, including conventioanl chromophobe renal cell carcinoma(ChRCC), ChRCC with neuroendocrine differentiation and no-tumor region by 44k oligonucleotide-based array comparative genomic hybridization (array CGH). 2 cases of ChRCC(NOS) vs ChRCC with neuroendocrine differentiation
Project description:In this study, we investigated CNAs of 4 tumor samples from 2 patients, including conventioanl chromophobe renal cell carcinoma(ChRCC), ChRCC with neuroendocrine differentiation and no-tumor region by 44k oligonucleotide-based array comparative genomic hybridization (array CGH).