Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

A clear picture of renal cell carcinoma

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

Subjects

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.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

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

References

  1. Zbar, B., Brauch, H., Talmadge, C. & Linehan, M. Nature 327, 721–724 (1987).

    Article  CAS  Google Scholar 

  2. Gnarra, J.R. et al. Nat. Genet. 7, 85–90 (1994).

    Article  CAS  Google Scholar 

  3. Herman, J.G. et al. Proc. Natl. Acad. Sci. USA 91, 9700–9704 (1994).

    Article  CAS  Google Scholar 

  4. Varela, I. et al. Nature 469, 539–542 (2011).

    Article  CAS  Google Scholar 

  5. Dalgliesh, G.L. et al. Nature 463, 360–363 (2010).

    Article  CAS  Google Scholar 

  6. Guo, G. et al. Nat. Genet. 44, 17–19 (2012).

    Article  CAS  Google Scholar 

  7. Sato, X. et al. Nat. Genet. 45, 860–867 (2013).

    Article  CAS  Google Scholar 

  8. The Cancer Genome Atlas Research Network. Nature published online; doi:10.1038/nature12222 (23 June 2013).

  9. Linehan, W.M., Srinivasan, R. & Schmidt, L.S. Nat. Rev. Urol. 7, 277–285 (2010).

    Article  CAS  Google Scholar 

  10. Kapur, P. et al. Lancet Oncol. 14, 159–167 (2013).

    Article  CAS  Google Scholar 

  11. Hakimi, A.A. et al. Eur. Urol. 63, 848–854 (2013).

    Article  Google Scholar 

  12. Hakimi, A.A. et al. Clin. Cancer Res. 19, 3259–3267 (2013).

    Article  CAS  Google Scholar 

  13. Shen, C. et al. Cancer Discov. 1, 222–235 (2011).

    Article  CAS  Google Scholar 

  14. Yang, H. et al. Nature 497, 217–223 (2013).

    Article  CAS  Google Scholar 

  15. Motzer, R.J. et al. Lancet 372, 449–456 (2008).

    Article  CAS  Google Scholar 

Download references

Author information

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

Authors
  1. A Ari Hakimi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Can G Pham
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. James J Hsieh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to James J Hsieh.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

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

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng.2708

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing