Department of Dermatology, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel.
Sheba Cancer Research Center, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel.
Angiogenesis. 2018 May;21(2):287-298. doi: 10.1007/s10456-018-9595-8. Epub 2018 Feb 3.
Generalized lymphatic anomaly (GLA or lymphangiomatosis) is a rare disease characterized by a diffuse proliferation of lymphatic vessels in skin and internal organs. It often leads to progressive respiratory failure and death, but its etiology is unknown. Here, we isolated lymphangiomatosis endothelial cells from GLA tissue. These cells were characterized by high proliferation and survival rates, but displayed impaired capacities for migration and tube formation. We employed whole exome sequencing to search for disease-causing genes and identified a somatic mutation in NRAS. We used mouse and zebrafish model systems to initially evaluate the role of this mutation in the development of the lymphatic system, and we studied the effect of drugs blocking the downstream effectors, mTOR and ERK, on this disease.
淋巴管异常症（GLA 或淋巴管瘤病）是一种罕见疾病，其特征是皮肤和内脏器官中的淋巴管弥漫性增殖。它常导致进行性呼吸衰竭和死亡，但病因不明。在此，我们从 GLA 组织中分离出淋巴管瘤病内皮细胞。这些细胞具有高增殖和存活率，但迁移和管状形成能力受损。我们采用全外显子组测序寻找致病基因，并发现 NRAS 中的一个体细胞突变。我们使用小鼠和斑马鱼模型系统初步评估了该突变在淋巴管系统发育中的作用，并研究了阻断下游效应物 mTOR 和 ERK 的药物对该疾病的影响。
