EPAS1-mutated paragangliomas are associated with hemoglobin disorders. EPAS1-mutated paragangliomas are associated with hemoglobin disorders

This study reports a large series patients presenting EPAS1-mutated paraganglioma in whom we investigated a cause underlying chronic hypoxia. Four patients (10%) suffered from hypoxemic heart disease. In patients with available hemoglobin electrophoresis results, 59% presented a hemoglobin disorder. Histological and transcriptomic characterization of EPAS1-tumors revealed increased angiogenesis and high similarities with pseudohypoxic paragangliomas caused by VHL gene mutations. Overall design: To investigate the transcriptomic characterization of EPAS1-related paragangliomas we performed gene expression profiling analysis using data obtained from RNA sequencing for 52 paragangliomas with various genotypes including 19 EPAS1 (including one tumor in duplicate), 6 SDHx, 2 SLC25A11, 6 VHL, 3 RET, 3 NF1, 1 MAX, 1 MAML3 and 11 unmutated paragangliomas.

本研究报道了一系列携带EPAS1突变的副神经节瘤（Paraganglioma）患者，并对其慢性缺氧的潜在病因展开了探究。其中4例患者（占比10%）并发低氧性心脏病。在具备血红蛋白电泳检测结果的患者中，59%存在血红蛋白异常。对EPAS1突变型肿瘤的组织学与转录组学特征分析显示，其血管生成能力增强，且与VHL基因突变所致的假性缺氧型副神经节瘤具有高度相似性。整体实验设计：为探究EPAS1相关副神经节瘤的转录组学特征，本研究基于52例不同基因型副神经节瘤的RNA测序数据开展基因表达谱分析，所纳入的样本包括19例EPAS1突变型（含1例重复检测的肿瘤样本）、6例SDHx突变型、2例SLC25A11突变型、6例VHL突变型、3例RET突变型、3例NF1突变型、1例MAX突变型、1例MAML3突变型以及11例未携带相关突变的副神经节瘤样本。