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Clear Cell Renal Cell Carcinoma Study

What is kidney cancer?

The most common type of kidney cancer is called renal cell carcinoma. This cancer forms in the cells lining the small tubules in the kidney that filter waste from the blood and make urine. An estimated 58,240 Americans were expected to have been diagnosed with kidney cancer and an estimated 13,040 to have died of this cancer in 2010.1 Most people with kidney cancer are usually over 55 years of age and this cancer is more common in men. When detected early, most cases of kidney cancer can be treated effectively. However, survival rates are low when the cancer has spread from the kidney to other parts of the body. View additional information on kidney cancer.

TCGA analyzed two common subtypes of renal cell carcinoma: clear cell and papillary. The identification of these subtypes of kidney cancer is based on how the cancer cells look under a microscope. Approximately 92% of cases are clear cell carcinoma.2

What have TCGA researchers learned about clear cell renal cell carcinoma?

  • Molecular alterations in kidney clear cell carcinoma modulate cell signaling:
    • Clear cell carcinoma tumors contained frequent alterations in VHL and its interaction partners, genes involved in cellular oxygen sensing.
    • Genes of the PI(3)K/AKT pathway were highly mutated, suggesting that tumors may respond to specific inhibitors of this pathway.
    • SETD2 was frequently mutated, leading to global hypomethylation and vast changes in gene expression.
  • Altered cellular metabolism distinguished clear cell carcinoma from other cancers:
    • A shift to favor certain metabolic pathways and reduce the use of others was associated with poor outcomes.
    • In some cases, a metabolic shift may be caused by changes in the PI3K/AKT/mTOR pathway, which was altered in 28% of cases.
  • Clear cell carcinomas may be categorized into four subtypes based on mRNA and microRNA expression, each subtype associated with differential survival.
Selected References
  1. American Cancer Society. Cancer Facts and Figures 2010. Atlanta: American Cancer Society, Inc. 2010. 

  2. Chow WH, Dong LM, and Devesa SS. Epidemiology and risk factors for kidney cancer. Nat Rev Urol. 2010 May; 7(5):245-57.

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