Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2013 Jun;20(3):186-91.
doi: 10.1097/MED.0b013e32835fcc45.

Genetics of pheochromocytoma and paraganglioma syndromes: new advances and future treatment options

Ales Vicha  1 , Zdenek Musil, Karel Pacak
Affiliations
Review

Genetics of pheochromocytoma and paraganglioma syndromes: new advances and future treatment options

Ales Vicha et al. Curr Opin Endocrinol Diabetes Obes. 2013 Jun.

Abstract

Purpose of review: To summarize the recent advances in the genetics of pheochromocytoma and paraganglioma (PHEO/PGL), focusing on the new susceptibility genes and dividing PHEOs/PGLs into two groups based on their transcription profile.

Recent findings: Recently, TMEM127, MYC-associated factor X, and hypoxia-inducible factor (HIF) 2α have been described in the pathogenesis of PHEOs/PGLs. Thus, now about 30-40% of these tumors are linked to the germline mutations, which also include mutations in the VHL, RET, NF1, SDHx, and SDHAF2 genes. Furthermore, PHEOs/PGLs have been divided into two groups, cluster 1 (SDHx/VHL) and cluster 2 (RET/NF1), based on the transcription profile revealed by genome-wide expression microarray analysis.

Summary: PHEOs/PGLs are the most inherited tumors among (neuro)endocrine tumors. Future approaches in genetics, including whole-genome sequencing, will allow the discovery of additional PHEO/PGL susceptibility genes. The current division of PHEOs/PGLs into cluster 1 and 2 provides us with additional knowledge related to the pathogenesis of these tumors, including the introduction of new treatment options for patients with metastatic PHEOs/PGLs. New discoveries related to the role of the HIF-1/HIF-2α genes in the pathogenesis of almost all inherited PHEOs/PGLs may call for a new regrouping of these tumors and discoveries of new treatment targets.

PubMed Disclaimer

Conflict of interest statement

Conflicts of interest

There are no conflicts of interest.

References

    1. Pacak K. Phaeochromocytoma: a catecholamine and oxidative stress disorder. Endocr Regul. 2011;45:65–90. - PMC - PubMed
    1. Papaspyrou K, Mewes T, Rossmann H, et al. Head and neck paragangliomas: report of 175 patients. Head Neck. 2012;34:632–637. - PubMed
    1. Neumann HP, Bausch B, McWhinney SR, et al. Germ-line mutations in nonsyndromic pheochromocytoma. N Engl J Med. 2002;346:1459–1466. - PubMed
    1. Erlic Z, Rybicki L, Peczkowska M, et al. Clinical predictors and algorithm for the genetic diagnosis of pheochromocytoma patients. Clin Cancer Res. 2009;15:6378–6385. - PubMed

    1. Gimenez-Roqueplo AP, Dahia PL, Robledo M. An update on the genetics of paraganglioma, pheochromocytoma, and associated hereditary syndromes. Horm Metab Res. 2012;44:328–333. This review explains the division of PHEO/PGL into two clusters.

Publication types

MeSH terms