Nature. Volume 499: p43-49, 04 July 2013 10.1038/nature12222
Genetic changes underlying clear cell renal cell carcinoma (ccRCC) include alterations in genes controlling cellular oxygen sensing (for example, VHL) and the maintenance of chromatin states (for example, PBRM1). We surveyed more than 400 tumours using different genomic platforms and identified 19 significantly mutated genes. The PI(3)K/AKT pathway was recurrently mutated, suggesting this pathway as a potential therapeutic target. Widespread DNA hypomethylation was associated with mutation of the H3K36 methyltransferase SETD2, and integrative analysis suggested that mutations involving the SWI/SNF chromatin remodelling complex (PBRM1, ARID1A, SMARCA4) could have far-reaching effects on other pathways. Aggressive cancers demonstrated evidence of a metabolic shift, involving downregulation of genes involved in the TCA cycle, decreased AMPK and PTEN protein levels, upregulation of the pentose phosphate pathway and the glutamine transporter genes, increased acetyl-CoA carboxylase protein, and altered promoter methylation of miR-21 (also known as MIR21) and GRB10. Remodelling cellular metabolism thus constitutes a recurrent pattern in ccRCC that correlates with tumour stage and severity and offers new views on the opportunities for disease treatment.
Data in the GDC
- GDC Manifests
- Open-Access Data - Download Manifest (40 Files)
- Controlled-Access Data - Download Manifest (2 Files)
Supplemental Data
These data represent a data freeze from April 19, 2012.
- Sample Lists - below are links to cumulative list of samples for the population
- Mutations
- Level 2 Data Archives - Somatic MAF file [maf] - Exome-based somatic mutations
- Supplementary Data - BAM file list [txt] - Exome sequence BAM file references
- Whole Genome Sequencing
- Supplementary Data - Whole genome sequencing cases [xlsx]
- SNP and Copy Number
- Level 1 Data Archives
- MAGE-TAB Archives
- Supplementary Data
- Segmented data [gz]
- Summary of GISTIC results [zip]
- Genes in amplification peaks [txt]
- Genes in deletion peaks [txt]
- Copy numbers for every gene [zip]
- Amplification and deletion calls for every gene [zip]
- Copy numbers for every gene from just arm-level events [zip]
- Copy numbers for every gene from just focal events [zip]
- Segmentation file for only focal events [txt]
- Purity estimates [txt]
- Gene Expression
- Level 3 Data Archives
- MAGE-TAB Archives
- Supplementary Data
Data Matrix Files
- miRNA Expression
- Level 3 Data Archives
- MAGE-TAB Archives
- Supplementary Data
Data Matrix Files
Normalized to reads per million (RPM) mapped to miRBase v16 annotations:
- DNA Methylation
- Level 3 Data Archives
- MAGE-TAB Archives
- Supplementary Data
- Hypermethylation index per tumor [txt] - A hypermethylation index for each tumor, representing degree of hypermethylation (percentage methylated) at 15,101 CpG loci that show cancer specific hypermethylation
- Gene X Sample Matrix for 290 epigenetically silenced genes in 5% of the samples [csv]
- Reverse Phase Protein Array (RPPA)
- Supplementary Data
- Full RPPA data [xls] (13.3M)
- Median-centered RPPA data [txt] (1.0M)
- Supplementary Data
- Clinical
- Level 1 Data Archives
- Supplementary Data - Data matrix of clinical values [xlsx]
Additional Resources
- cBio Cancer Genomics Portal for Kidney Renal Clear Cell Carcinoma at MSKCC
- GDC Encyclopedia
- Descriptions of TCGA data are provided in the TCGA Barcode Encyclopedia Page
- Genomic Data Commons Portal
Instructions for Data Download
Open Access Data
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Controlled Access Data
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- GDC DTT (Download, User’s Guide)
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