Gorham–Stout disease (GSD), a rare disorder of unknown etiology, is characterized by massive osteolysis that is associated with proliferation and dilation of lymphatic vessels. Variants in cancer-associated genes have been described in complex lymphatic anomalies. To explore the pathogenesis of GSD, we performed the amplicon-based deep sequencing on 50 cancer-related genes to assay affected tissues from the six patients with GSD. In one patient, a somatic activating KRAS c.182A > G variant (p.Q61R) was detected in 1% of the tissue sample. Conversely, the mutant allele was not detected in uninvolved normal skin and blood samples. Histopathology of the patient’s tissue sample showed proliferation of abnormal lymphatic and blood vascular endothelial cells, osteoclasts, and activated macrophages. The activating KRAS variant is a known ‘hotspot’ variant, frequently identified in several types of human cancer. This is the first report of identifying a pathogenic variant in a patient with GSD. This finding may set the stage for elucidation of pathophysiology and the development of novel therapies for GSD.

Gorham–Stout病（GSD）是一种罕见的病因不明的罕见疾病，其特征是大量溶骨与淋巴管的增生和扩张有关。已经在复杂的淋巴异常中描述了癌症相关基因的变异。为了探讨GSD的发病机理，我们对50个与癌症相关的基因进行了基于扩增子的深度测序，以分析6名GSD患者的受影响组织。在一名患者中，在1％的组织样本中检测到了体细胞激活的KRAS c.182A> G变体（p.Q61R）。相反，在未涉及的正常皮肤和血液样本中未检测到突变等位基因。患者组织样品的组织病理学显示异常淋巴和血管内皮细胞，破骨细胞和活化的巨噬细胞增殖。激活KRAS变体是一种已知的“热点”变体，经常在几种类型的人类癌症中发现。这是鉴定GSD患者病原体变异的第一份报告。这一发现可能为阐明病理生理学和开发GSD新疗法奠定基础。