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Review
. 2023 Mar 8;30(4):e220373.
doi: 10.1530/ERC-22-0373. Print 2023 Apr 1.

Update on the genetics of paragangliomas

Anne-Paule Gimenez-Roqueplo  1   2 , Mercedes Robledo  3   4 , Patricia L M Dahia  5   6
Affiliations
Review

Update on the genetics of paragangliomas

Anne-Paule Gimenez-Roqueplo et al. Endocr Relat Cancer. .

Abstract

Paragangliomas (PGL) of the adrenal (also known as pheochromocytomas) or extra-adrenal neural crest-derived cells are highly heritable tumors, usually driven by single pathogenic variants that occur mutually exclusively in genes involved in multiple cellular processes, including the response to hypoxia, MAPK/ERK signaling, and WNT signaling. The discovery of driver mutations has led to active clinical surveillance with outcome implications in familial PGL. The spectrum of mutations continues to grow and reveal unique mechanisms of tumorigenesis that inform tumor biology and provide the rationale for targeted therapy. Here we review recent progress in the genetics and molecular pathogenesis of PGLs and discuss new prospects for advancing research with new disease models and ongoing clinical trials presented at the recent International Symposium of Pheochromocytomas and Paragangliomas (ISP2022) held in October 2022 in Prague.

Keywords: germline mutations; paraganglioma; pheochromocytoma; somatic mutations; susceptibility genes.

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Conflict of interest statement

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of this review.

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