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EPAS1-mutated paragangliomas associated with haemoglobin disorders.

Maxence ManciniAlexandre BuffetBaptiste PorteLaurence AmarCharlotte Lussey-LepoutreLise CrinièreEric BaudinTchao MeatchiAnne-Paule Gimenez-RoqueploJudith FavierNelly Burnichon
Published in: British journal of haematology (2024)
We report a large series of 40 patients presenting EPAS1-mutated paraganglioma (PGL) in whom we investigated a cause underlying chronic hypoxia. Four patients suffered from hypoxaemic heart disease. In patients with available haemoglobin electrophoresis results, 59% presented with a haemoglobin disorder, including six with sickle cell disease, five with sickle cell trait and two with heterozygous haemoglobin C disease. Histological and transcriptomic characterization of EPAS1 tumours revealed increased angiogenesis and high similarities with pseudohypoxic PGLs caused by VHL gene mutations. Sickle haemoglobinopathy carriers could thus be at increased risk for developing EPAS1-PGLs, which should be taken into account in their management and surveillance.
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