New Insights on the Genetics of Pheochromocytoma and Paraganglioma and Its Clinical Implications

Sakshi Jhawar; Yasuhiro Arakawa; Suresh Kumar; Diana Varghese; Yoo Sun Kim; Nitin Roper; Fathi Elloumi; Yves Pommier; Karel Pacak; Jaydira Del Rivero

doi:10.3390/cancers14030594

New Insights on the Genetics of Pheochromocytoma and Paraganglioma and Its Clinical Implications

Cancers (Basel). 2022 Jan 25;14(3):594. doi: 10.3390/cancers14030594.

Authors

Affiliations

¹ Life Bridge Health Center, Internal Medicine Program, Sinai Hospital of Baltimore, Baltimore, MD 21215, USA.
² Developmental Therapeutics Branch, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD 20892, USA.
³ Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (NIH), Bethesda, MD 20892, USA.

Abstract

Pheochromocytomas (PHEOs) and paragangliomas (PGLs) are rare neuroendocrine tumors that arise from chromaffin cells. PHEOs arise from the adrenal medulla, whereas PGLs arise from the neural crest localized outside the adrenal gland. Approximately 40% of all cases of PPGLs (pheochromocytomas/paragangliomas) are associated with germline mutations and 30-40% display somatic driver mutations. The mutations associated with PPGLs can be classified into three groups. The pseudohypoxic group or cluster I includes the following genes: SDHA, SDHB, SDHC, SDHD, SDHAF2, FH, VHL, IDH1/2, MHD2, EGLN1/2 and HIF2/EPAS; the kinase group or cluster II includes RET, NF1, TMEM127, MAX and HRAS; and the Wnt signaling group or cluster III includes CSDE1 and MAML3. Underlying mutations can help understand the clinical presentation, overall prognosis and surveillance follow-up. Here we are discussing the new genetic insights of PPGLs.

Keywords: genetics; germline; paraganglioma; pheochromocytoma; screening.

Publication types

Review