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

Vicha A, Musil Z, Pacak K

Curr Opin Endocrinol Diabetes Obes. 2013 Mar 11

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) 2? 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-2? 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.

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PMID: 23481210 [PubMed - as supplied by publisher]