Unknown,Transcriptomics,Genomics,Proteomics

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Patterns of gene expression and copy-number alterations in VHL disease-associated and sporadic ccRCC


ABSTRACT: Recent insights into the role of the VHL tumor suppressor gene in hereditary and sporadic clear cell carcinoma of the kidney (ccRCC) have led to new treatments for patients with metastatic ccRCC, although virtually all patients eventually succumb to the disease. We performed an integrated, genome-wide analysis of copy-number changes and gene expression profiles in 90 tumors, including both sporadic and VHL disease-associated tumors, in hopes of identifying new therapeutic targets in ccRCC. We identified 14 regions of nonrandom copy-number change, including 7 regions of amplification (1q, 2q, 5q, 7q, 8q, 12p, and 20q) and 7 regions of deletion (1p, 3p, 4q, 6q, 8p, 9p, and 14q). An analysis aimed at identifying the relevant genes revealed VHL as one of 3 genes in the 3p deletion peak, CDKN2A and CDKN2B as the only genes in the 9p deletion peak, and MYC as the only gene in the 8q amplification peak. An integrated analysis to identify genes in amplification peaks that are consistently overexpressed among amplified samples confirmed MYC as a potential target of 8q amplification and identified candidate oncogenes in the other regions. A comparison of genomic profiles revealed that VHL disease-associated tumors are similar to a subgroup of sporadic tumors, and thus more homogeneous overall. Sporadic tumors without evidence of biallelic VHL inactivation fell into 2 groups: one group with genomic profiles highly dissimilar to the majority of ccRCC, and a second group with genomic profiles that are much more similar to tumors with biallelic inactivation of VHL. Keywords: comparative genomic hybridization 90 clear cell renal cell carcinomas and 21 renal cancer cell lines were subject to 250K SNP analysis.

ORGANISM(S): Homo sapiens

DISEASE(S): normal renal cortex

SUBMITTER: Sabina Signoretti 

PROVIDER: E-GEOD-14994 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Patterns of gene expression and copy-number alterations in von-hippel lindau disease-associated and sporadic clear cell carcinoma of the kidney.

Beroukhim Rameen R   Brunet Jean-Philippe JP   Di Napoli Arianna A   Mertz Kirsten D KD   Seeley Apryle A   Pires Maira M MM   Linhart David D   Worrell Robert A RA   Moch Holger H   Rubin Mark A MA   Sellers William R WR   Meyerson Matthew M   Linehan W Marston WM   Kaelin William G WG   Signoretti Sabina S  

Cancer research 20090601 11


Recent insights into the role of the von-Hippel Lindau (VHL) tumor suppressor gene in hereditary and sporadic clear-cell renal cell carcinoma (ccRCC) have led to new treatments for patients with metastatic ccRCC, although virtually all patients eventually succumb to the disease. We performed an integrated, genome-wide analysis of copy-number changes and gene expression profiles in 90 tumors, including both sporadic and VHL disease-associated tumors, in hopes of identifying new therapeutic target  ...[more]

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