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Series GSE36895 Query DataSets for GSE36895
Status Public on Jun 10, 2012
Title Molecular Genetic Classification of clear-cell Renal Cell Carcinoma (ccRCC) based on the Gene Expression Profiling of Tumors and Tumorgrafts deficient for BAP1 or PBRM1
Organism Homo sapiens
Experiment type Expression profiling by 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 exhibited similar gene expression profiling to corresponding primary tumors. Gene expression profiling of tumors and tumorgrafts displayed different signatures for BAP1- and PBRM1-deficient samples. 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 RNA of clear-cell renal cell carcinoma (ccRCC) primary tumors, tumors growing in immunodeficient mice (tumorgrafts), and normal kidney cortices were labeled and hybridized to Affymetrix Human Genome U133 Plus 2.0 arrays.
Contributor(s) Peña-Llopis S, Brugarolas J
Citation(s) 22683710, 24136348
Submission date Mar 28, 2012
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 (1)
GPL570 [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array
Samples (76)
GSM904985 Normal cortex of patient 14
GSM904986 ccRCC tumor of patient 14
GSM904988 Normal cortex of patient 26
BioProject PRJNA157021

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Supplementary file Size Download File type/resource
GSE36895_RAW.tar 465.7 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

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