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Paraganglioma & Pheochromocytoma Study

What are paraganglioma and pheochromocytoma?

Paraganglioma is a rare cancer that originates in the nerve cells of the adrenal glands, organs on top of each kidney that produce important hormones. Paraganglioma that develops in the center of the adrenal gland is called pheochromocytoma. Paraganglioma that forms outside of the adrenal gland, often along blood vessels and nerves in the head and neck, is called extra-adrenal paraganglioma, or simply paraganglioma.

Each year, between 2 and 8 people per million worldwide are diagnosed with paraganglioma and pheochromocytoma.1 10% of all cases occur in children.2 In both adults and children, pheochromocytoma is more common than paraganglioma.2 No known environmental, dietary, or lifestyle risk factors have been associated with these cancers.

However, paraganglioma and pheochromocytoma can be hereditary diseases.3 A study reported that about 41% of patients diagnosed with one of these diseases in the U.S. carry inherited genetic mutations that increase the risk of malignancy.1 TCGA studied both hereditary and non-hereditary (also called sporadic) paraganglioma and pheochromocytoma. When the cancer spreads to other parts of the body, only 44% of patients survive five years after their diagnosis.2 Additional information on paraganglioma and pheochromocytoma.

What have TCGA researchers learned about paraganglioma and pheochromocytoma?

  • Identified novel, non-inherited, genomic changes underlying pheochromocytomas (PCC) and paragangliomas (PGL) in the most comprehensive study to date.
  • Mutations in the gene CSDE1, which prevents the cell from destroying itself when its behavior becomes abnormal, plays a significant role in allowing PCC and PGL cells to grow and thrive.
    • This is the first study to identify CSDE1 as a key cancer gene.
  • Fusions involving the gene MAML3, which contributes to cell proliferation, activates the Wnt signaling pathway and leads to cell growth and metastasis.
  • PCC and PGL may be subtyped into four groups based on genomic alterations including:
    • Wnt-altered, a novel subtype containing CSDE1 and MAML3 alterations, was associated with the shortest survival
    • Cortical admixture, a novel subtype displaying increased expression adrenal cortex genes
    • Kinase signaling and pseudohypoxia, two previously defined subtypes
Selected References
  1. Fishbein L, Merrill S, Fraker DL et al. Inherited mutations in pheochromocytoma and paraganglioma: why all patients should be offered genetic testing. Ann Surg Oncol. 2013 May; 20(5):1444-50.

  2. Hanna NN, and Kenady DE: Pheochromocytoma. In: Holzheimer RG and Mannick JA, ed. Surgical treatment: evidence-based and problem-oriented. Munich: Zuckschwerdt, 2001.

  3. U.S. National Library of Medicine. Hereditary paraganglioma-pheochromocytoma. Genetics Home Reference. Accessed 2013.  

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