ArticleThe Journal of clinical endocrinology and metabolism2023
Somatic EPAS1 Variants in Pheochromocytoma and Paraganglioma in Patients With Sickle Cell Disease.
Article in The Journal of clinical endocrinology and metabolism, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 8 citations in OpenAlex.
- Genetic, cellular, and environmental factors influencing tumourigenesis in carriers of succinate dehydrogenase germline mutations.Endocrine-related cancer · 2026Review
- A novel activating somatic mutation in EPAS1, coding for HIF-2α, in a patient with a paraganglioma and sickle cell disease.Archives of endocrinology and metabolism · 2026Article
- Convergent Genetic Adaptation in Human Tumors Developed Under Systemic Hypoxia and in Populations Living at High Altitudes.Cancer discovery · 2025Article
- Sex- and Ethnicity-related Differences in Pheochromocytoma/Paraganglioma.Journal of the Endocrine Society · 2024Article
- Patient Sex and Origin Influence Distribution of Driver Genes and Clinical Presentation of Paraganglioma.Journal of the Endocrine Society · 2024Article
- Somatic EPAS1 Variants in Pheochromocytoma and Paraganglioma in Patients With Sickle Cell Disease.The Journal of clinical endocrinology and metabolism · 2023Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
contextSomatic EPAS1 variants account for 5% to 8% of all pheochromocytoma and paragangliomas (PPGL) but are detected in over 90% of PPGL in patients with congenital cyanotic heart disease, where hypoxemia may select for EPAS1 gain-of-function variants. Sickle cell disease (SCD) is an inherited hemoglobinopathy associated with chronic hypoxia and there are isolated reports of PPGL in patients with SCD, but a genetic link between the conditions has yet to be established.
objectiveTo determine the phenotype and EPAS1 variant status of patients with PPGL and SCD.
methodsRecords 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.
resultsFour 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.
conclusionWe 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.
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