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Series GSE25540 Query DataSets for GSE25540
Status Public on Jun 10, 2012
Title DNA Copy-Number Alterations in clear-cell Renal Cell Carcinoma (ccRCC) Tumors and Tumorgrafts for samples deficient in BAP1 or PBRM1
Organism Homo sapiens
Experiment type Genome variation profiling by SNP array
Summary Renal cell carcinoma (RCC) exhibits some unusual features and genes commonly mutated in cancer are rarely mutated in clear-cell RCC (ccRCC), the most common type. The most prevalent genetic alteration in ccRCC is the inactivation of the tumor suppressor gene VHL. Using whole-genome and exome sequencing we discovered BAP1 as a novel tumor suppressor in ccRCC that shows little overlap with mutations in PBRM1, another recent tumor suppressor. Whereas VHL was mutated in 81% of the patients (142/176), PBRM1 was lost in 58% and BAP1 in 15% of the patients analyzed. All these tumor suppressor genes are located in chromosome 3p, which is partially or completely lost in most ccRCC patients. However, BAP1 but not PBRM1 loss was associated with higher Fuhrman grade and, therefore, poorer outcome. Xenograft tumors (tumorgrafts) implanted orthotopically in mice retained >92% of mutations and exhibited similar DNA copy number alterations to corresponding primary tumors. Thus, after inactivation of VHL, the acquisition of a mutation in BAP1 or PBRM1 defines a different program that might alter the fate of the patient. Our results establish the foundation for an integrated pathological and molecular genetic classification of about 70% of ccRCC patients, paving the way for subtype-specific treatments exploiting genetic vulnerabilities.
Overall design The genomic DNA of clear-cell renal cell carcinoma (ccRCC) primary tumors, tumors growing in immunodeficient mice (tumorgrafts), and normal samples were labeled and hybridized to Affymetrix SNP arrays 6.0.
Contributor(s) Peña-Llopis S, Brugarolas J
Citation(s) 22683710, 24136348
Submission date Nov 22, 2010
Last update date Jul 31, 2019
Contact name Samuel Peña-Llopis
Phone (01) 214-648-4099
Fax (01) 214-648-1960
Organization name UT Southwestern Medical Center
Department Internal Medicine - Oncology Division
Lab Brugarolas Lab
Street address 6000 Harry Hines Blvd., NB5.102
City Dallas
State/province TX
ZIP/Postal code 75390-9133
Country USA
Platforms (2)
GPL6801 [GenomeWideSNP_6] Affymetrix Genome-Wide Human SNP 6.0 Array
GPL6984 Illumina Human1M-Duov3 DNA Analysis BeadChip (Human1M-Duov3_B)
Samples (82)
GSM627709 ccRCC tumor of patient T22 (Affymetrix)
GSM627710 Mouse tumorgraft, cohort 0 of patient T22 (Affymetrix)
GSM627750 Blood sample of patient T22 (Affymetrix)
BioProject PRJNA134015

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE25540_RAW.tar 3.5 Gb (http)(custom) TAR (of CEL, CHP, TXT)
Processed data included within Sample table
Processed data provided as supplementary file

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