Pheochromocytomas/paragangliomas have a distinct molecular landscape that allows them to be classified into clusters based on underlying genetic changes. Pheochromocytomas/paragangliomas have the greatest incidence of heritability among all cancers, with roughly 30% to 35% of Caucasian patients (a lesser percentage in the population) having germline mutations in susceptibility genes. Somatic driver mutations afflict 35% to 40% of Caucasian individuals (a more significant incidence in the population).
Thus, approximately 70% of all patients with pheochromocytoma/paraganglioma may be classified into one of three major genetic clusters with distinct phenotypic and clinical behavior. Krebs cycle/VHL/EPAS1-related cluster 1 cancers have a noradrenergic biochemical profile and need constant monitoring due to the risk of metastasis and recurrence. Cluster 2 tumors linked to kinase signaling, on the other hand, have an adrenergic phenotype, episodic symptoms, and a less aggressive trajectory. The clinical correlations of Wnt signaling–related cluster 3 tumors are still unknown. However, aggressive behavior appears to be a possibility. For a study, researchers examined and explained why cluster-specific (personalized) management of pheochromocytoma/paraganglioma was critical for determining clinical behavior and prognosis, guiding individual diagnostic procedures (biochemical interpretation, selection of the most sensitive imaging modalities), and providing personalized management and follow-up in this review.
Although cluster-specific therapy for inoperable/metastatic illness had not yet become standard practice, they believed that educated tailored genetic-driven treatment was the appropriate next step. Therefore, the evaluation combined published recommendations and expert opinions within each cluster to create a cohesive tailored patient care plan.
Reference:academic.oup.com/edrv/article/43/2/199/6306512
