嗜铬细胞瘤和副神经节瘤的遗传学。
Genetics of pheochromocytoma and paraganglioma.
机构信息
Hospital of the University of Pennsylvania, Department of Surgery, Division of Endocrine and Oncologic Surgery and the Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
University of Colorado School of Medicine, Department of Medicine, Division of Endocrinology, Metabolism and Diabetes and the Division of Biomedical Informatics and Personalized Medicine, University of Colorado, Aurora, Colorado, USA.
出版信息
Curr Opin Endocrinol Diabetes Obes. 2021 Jun 1;28(3):283-290. doi: 10.1097/MED.0000000000000634.
PURPOSE OF REVIEW
This review summarizes our current understanding of germline and somatic genetics and genomics of pheochromocytomas and paragangliomas (PCC/PGL), describes existing knowledge gaps, and discusses future research directions.
RECENT FINDINGS
Germline pathogenic variants (PVs) are found in up to 40% of those with PCC/PGL. Tumors with germline PVs are broadly categorized as Cluster 1 (pseudohypoxia), including those with SDH, VHL, FH, and EPAS1 PVs, or Cluster 2 (kinase signaling) including those with NF1, RET, TMEM127, and MAX PVs. Somatic driver mutations exist in some of the same genes (RET, VHL, NF1, EPAS1) as well as in additional genes including HRAS, CSDE1 and genes involved in cell immortalization (ATRX and TERT). Other somatic driver events include recurrent fusion genes involving MAML3.
SUMMARY
PCC/PGL have the highest association with germline PVs of all human solid tumors. Expanding our understanding of the molecular pathogenesis of PCC/PGL is essential to advancements in diagnosis and surveillance and the development of novel therapies for these unique tumors.
目的综述
本文总结了嗜铬细胞瘤和副神经节瘤（PCC/PGL）种系和体细胞遗传学及基因组学的现有认识，描述了目前存在的知识空白，并讨论了未来的研究方向。
最近的发现
高达 40%的 PCC/PGL 患者存在种系致病性变异（PV）。具有种系 PV 的肿瘤广泛分为 1 类（拟缺氧），包括具有 SDH、VHL、FH 和 EPAS1 PV 的肿瘤，或 2 类（激酶信号），包括具有 NF1、RET、TMEM127 和 MAX PV 的肿瘤。一些相同基因（RET、VHL、NF1、EPAS1）以及其他基因（HRAS、CSDE1 和参与细胞永生化的基因（ATRX 和 TERT）存在体细胞驱动突变。其他体细胞驱动事件包括涉及 MAML3 的复发性融合基因。
总结
PCC/PGL 是所有人类实体瘤中与种系 PV 相关性最高的肿瘤。加深对 PCC/PGL 分子发病机制的理解对于这些独特肿瘤的诊断和监测的进展以及新疗法的开发至关重要。
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