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Review
. 2021 Jun 1;28(3):283-290.
doi: 10.1097/MED.0000000000000634.

Genetics of pheochromocytoma and paraganglioma

Heather Wachtel  1 , Lauren Fishbein  2
Affiliations
Review

Genetics of pheochromocytoma and paraganglioma

Heather Wachtel et al. Curr Opin Endocrinol Diabetes Obes. .

Abstract

Purpose of review: This review summarizes our current understanding of germline and somatic genetics and genomics of pheochromocytomas and paragangliomas (PCC/PGL), describes existing knowledge gaps, and discusses future research directions.

Recent findings: Germline pathogenic variants (PVs) are found in up to 40% of those with PCC/PGL. Tumors with germline PVs are broadly categorized as Cluster 1 (pseudohypoxia), including those with SDH, VHL, FH, and EPAS1 PVs, or Cluster 2 (kinase signaling) including those with NF1, RET, TMEM127, and MAX PVs. Somatic driver mutations exist in some of the same genes (RET, VHL, NF1, EPAS1) as well as in additional genes including HRAS, CSDE1 and genes involved in cell immortalization (ATRX and TERT). Other somatic driver events include recurrent fusion genes involving MAML3.

Summary: PCC/PGL have the highest association with germline PVs of all human solid tumors. Expanding our understanding of the molecular pathogenesis of PCC/PGL is essential to advancements in diagnosis and surveillance and the development of novel therapies for these unique tumors.

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