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Detection of tetraploidization in chromophobe renal cell carcinoma: insights and pitfalls [Agilent CGH]

ABSTRACT: Detection of tetraploidization in chromophobe renal cell carcinoma.

ORGANISM(S): Homo sapiens

PROVIDER: GSE131200 | GEO | 2019/05/15

REPOSITORIES: GEO

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Detection of tetraploidization in chromophobe renal cell carcinoma: insights and pitfalls [Agilent CGH]

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Project description:Chromophobic renal cell carcinomas (chRCC) typically have a hypodiploid genome, including a loss of chromosomes 1, 2, 6, 10, 13, 17 and 21, but few cases in the literature showed a gain of many chromosomes, suggesting a tetraploidy. The detection of this characteristic performed by comparative genomic hybridization (CGH-array), is very helpful for the diagnosis. To better characterize the phenomenon of tetraploidization and to explore the consequence and the difficulties of its detection, we studied a subset of 26 chRCC, including five cases of tetraploid chRCC, for which complementary analyses were performed. Our main objective was to determine whether these four cases displayed chromosomal losses typical of chRCC whitin a near-polyploid genome instead within a near-diploid one. We discuss the hazards and limitations of different molecular methods in the detection of polyploidization and its potential clinical consequences. In our study we show that this phenomenon of tetraploidization affects about 19% of chRCC and that is probably overlooked using standard molecular methods. The potential clinical consequences of this phenomenon are not identified yet.

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Gene Expression Profiling Separates Chromophobe Renal Cell Carcinoma from Oncocytoma

Project description:This study aims to compare gene expression profiles of chromophobe renal cell carcinoma (RCC) and benign oncocytoma, aiming at identifying differentially expressed genes.

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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.

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