Department of Medicine/Division of Hematology and Medical Oncology, Cancer Therapy and Research Center, Greehey Children Cancer Research Institute, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, Lab 5053-R3, MC 7880, San Antonio-TX 78229-3900, USA.
Nat Rev Cancer. 2014 Feb;14(2):108-19. doi: 10.1038/nrc3648. Epub 2014 Jan 20.
The neuroendocrine tumours pheochromocytomas and paragangliomas carry the highest degree of heritability in human neoplasms, enabling genetic alterations to be traced to clinical phenotypes through their transmission in families. Mutations in more than a dozen distinct susceptibility genes have implicated multiple pathways in these tumours, offering insights into kinase downstream signalling interactions and hypoxia regulation, and uncovering links between metabolism, epigenetic remodelling and cell growth. These advances extend to co-occurring tumours, including renal, thyroid and gastrointestinal malignancies. Hereditary pheochromocytomas and paragangliomas are powerful models for recognizing cancer driver events, which can be harnessed for diagnostic purposes and for guiding the future development of targeted therapies.
神经内分泌肿瘤嗜铬细胞瘤和副神经节瘤在人类肿瘤中具有最高的遗传性，使得通过家族遗传可以追踪到基因改变与临床表型的关系。十多个不同的易感基因的突变使这些肿瘤中的多个途径受到牵连，为激酶下游信号转导相互作用和低氧调节提供了深入了解，并揭示了代谢、表观遗传重塑和细胞生长之间的联系。这些进展还扩展到了伴发肿瘤，包括肾、甲状腺和胃肠道恶性肿瘤。遗传性嗜铬细胞瘤和副神经节瘤是识别癌症驱动事件的有力模型，可用于诊断目的，并为未来靶向治疗的发展提供指导。
