Comprehensive molecular characterization of clear cell renal cell carcinoma View Full Text


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Article Info

DATE

2013-07

AUTHORS

The Cancer Genome Atlas Research Network

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. More... »

PAGES

43

References to SciGraph publications

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    http://scigraph.springernature.com/pub.10.1038/nature12222

    DOI

    http://dx.doi.org/10.1038/nature12222

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1050842404

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/23792563


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