Conclusion
We propose that somatic EPAS1 variants may be acquired through exposure to chronic hypoxia in SCD and drive PPGL development. Future work is needed to further characterize this association.
Methods
Records of 128 patients with PPGL under follow-up at our center from January 2017 to December 2022 were screened for SCD diagnosis. For identified patients, clinical data and biological specimens were obtained, including tumor, adjacent non-tumor tissue and peripheral blood. Sanger sequencing of exons 9 and 12 of EPAS1, followed by amplicon next-generation sequencing of identified variants was performed on all samples.
Objective
To determine the phenotype and EPAS1 variant status of patients with PPGL and SCD.
Results
Four patients with both PPGL and SCD were identified. Median age at PPGL diagnosis was 28 years. Three tumors were abdominal paragangliomas and 1 was a pheochromocytoma. No germline pathogenic variants in PPGL-susceptibility genes were identified in the cohort. Genetic testing of tumor tissue detected unique EPAS1 variants in all 4 patients. Variants were not detected in the germline, and 1 variant was detected in lymph node tissue of a patient with metastatic disease.