Insights into Mechanisms of Pheochromocytomas and Paragangliomas Driven by Known or New Genetic Drivers

• Main Authors: Shahida K. Flores, Cynthia M. Estrada-Zuniga, Keerthi Thallapureddy, Gustavo Armaiz-Peña, Patricia L. M. Dahia
• Format: Article
• Language: English
• Published: MDPI AG 2021-09-01
• Series: Cancers
• Subjects: pheochromocytomas; paragangliomas; mutations; susceptibility genes; driver mutations; hereditary
• Online Access: https://www.mdpi.com/2072-6694/13/18/4602

Pheochromocytomas and paragangliomas are rare tumors of neural crest origin. Their remarkable genetic diversity and high heritability have enabled discoveries of bona fide cancer driver genes with an impact on diagnosis and clinical management and have consistently shed light on new paradigms in cancer. In this review, we explore unique mechanisms of pheochromocytoma and paraganglioma initiation and management by drawing from recent examples involving rare mutations of hypoxia-related genes <i>VHL, EPAS1</i> and <i>SDHB</i>, and of a poorly known susceptibility gene, <i>TMEM127.</i> These models expand our ability to predict variant pathogenicity, inform new functional domains, recognize environmental-gene connections, and highlight persistent therapeutic challenges for tumors with aggressive behavior.