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A clear picture of renal cell carcinoma

Nature Genetics volume 45, pages 849–850 (2013)Cite this article

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Two recent studies describe the largest molecular profiling analyses to date of clear-cell renal cell carcinoma (ccRCC) and report remarkably similar findings. The recurrent pathway alterations identified in these studies open new avenues for therapeutic advances in this chemotherapy- and radiation-resistant disease.

Renal cell carcinoma (RCC) is the eighth leading cause of cancer-related death in the United States and accounts for nearly 300,000 cases worldwide. RCC consists of several histological subtypes with distinct molecular alterations and clinical outcomes. ccRCC, characterized by high lipid and glycogen content that gives rise to its name, represents the most common and aggressive malignant subtype. For decades, ccRCC was defined by biallelic loss of VHL, which is located on chromosome 3p25. This biallelic loss occurs through 3p loss1 and concomitant VHL mutation2 or promoter methylation3. The VHL protein is an E3 ubiquitin ligase that ubiquitinates and targets hypoxia-inducible transcription factors (HIFs) for proteasome-mediated degradation. Thus, loss of VHL function leads to the stabilization and accumulation of HIFs that upregulate proangiogenic genes, most notably, VEGF (encoding vascular endothelial growth factor), thereby explaining the success of effective VEGF-targeted therapies in ccRCC.

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Figure 1: Integrated analyses of hundreds of ccRCC tumor samples identify recurrent pathway alterations.

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Authors and Affiliations

  1. A. Ari Hakimi, Can G. Pham and James J. Hsieh are at the Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.,

    A Ari Hakimi, Can G Pham & James J Hsieh

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  1. A Ari Hakimi
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  2. Can G Pham
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  3. James J Hsieh
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Correspondence to James J Hsieh.

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Hakimi, A., Pham, C. & Hsieh, J. A clear picture of renal cell carcinoma. Nat Genet 45, 849–850 (2013). https://doi.org/10.1038/ng.2708

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