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Comprehensive molecular characterization of clear cell renal cell carcinoma


Nature, Volume 499 Number 7456, July 4, 2013 [doi:10.1038/nature12222]

Abstract

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.

Associated Data Files

These data represent a data freeze from April 19, 2012. Please note that more recent data are available via the TCGA Data Portal

Sample Lists

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

    SNP and Copy Number

    Gene Expression

    miRNA Expression

    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

    Clinical

    Views of the Data

    Additional Information