Paragangliomas/Pheochromocytomas: clinically oriented genetic testing

Area of Science:

• Endocrinology
• Oncology
• Genetics

Background:

• Paragangliomas are rare neuroendocrine tumors originating from the sympathetic or parasympathetic nervous system.
• Sympathetic paragangliomas include pheochromocytomas (adrenal medulla) and other localizations, while parasympathetic types occur in the head and neck.
• Recent advances have significantly improved understanding of the familial forms of these tumors.

Purpose of the Study:

• To review the genetic and clinical aspects of syndromic and nonsyndromic pheochromocytoma/paraganglioma.
• To provide an updated overview of implicated genes and their roles.
• To propose an algorithm for genetic testing in affected patients.

Main Methods:

• Literature review of genetic and clinical studies on pheochromocytoma and paraganglioma.
• Analysis of known and novel genes associated with these tumors.
• Synthesis of information to guide genetic testing strategies.

Main Results:

• Classical syndromic forms are linked to VHL, RET, and NF1 genes.
• Ten novel genes (SDHA-D, SDHAF2, TMEM127, MAX, EGLN1, HIF2A, KIF1B) are implicated.
• Approximately 35% of cases result from germline mutations; somatic mutations are also detected in several genes.
• Identification of specific mutations aids in treatment decisions and follow-up.

Conclusions:

• Genetic testing is crucial for diagnosing and managing pheochromocytoma/paraganglioma.
• Understanding the genetic basis allows for tailored treatment and prognostic guidance.
• An updated genetic testing algorithm can improve patient care and outcomes.