PIK3CA相关过度生长谱：诊断和检测合格标准、鉴别诊断及其评估

PIK3CA编码磷脂酰肌醇3激酶（PI3K）的p110a亚基, 已被证实是一种癌基因。PIK3CA体细胞突变会使身体各部位节段性组织生长过度,导致如偏侧过度发育多发脂肪瘤病(HHML)、巨脑畸形-毛细血管畸形(MCAP)、CLOVES综合征等一系列相关罕见综合征。其临床表现独特而多样,但有些症状相互重叠,疾病命名也比较混乱。研究者对各综合征关注度的不同,导致目前文献出现认识偏倚,使得对PIK3CA基因型-表型的综合分析更加复杂。2013年9月11~12日,美国国立卫生研究院（NIH）在马里兰州贝塞斯达召开研讨会,就最新临床及分子学研究进展进行了深入探讨,对涵盖性术语“PIK3CA相关过度生长谱（PROS）”达成共识,提出了该谱系的关键临床诊断特征和检测标准,初步统一了过度生长的临床评估和分子学诊断方法,并提出组织过度生长和脉管异常的手术治疗、避免血栓形成的最佳措施以及潜在药物的开发等是未来亟待解决的问题。本文对会议成果做一介绍,为研究理清思路,并为临床医师诊疗、预测及设计靶向治疗临床试验提供参考。

PIK3CA-related overgrowth spectrum(PROS): Diagnostic and testing eligibility criteria,differential diagnosis,and evaluation

PIK3CA, which encodes phosphatidylinositol 3 kinase (PI3K) subunit p110a, has been identified as an oncogene. Somatic mutations in the PIK3CA gene cause heterogeneous segmental overgrowth of body tissues, displays as various phenotypes include hemihyperplasia multiple lipomatosis (HHML), megalencephaly-capillary malformation (MCAP), CLOVES syndrome et al. Clinical findings of these syndromes were distinct, but partially overlapping ,and its designations were non-uniformed. The distinct clinical focus of the investigators has led to ascertainment bias in the published literature, complicating a comprehensive assessment of genotype-phenotype correlation analysis. On September 11 and 12, 2013,a two-day workshop convened on the NIH campus in Bethesda, Maryland, discussed emerging clinical and molecular information on the phenotypes caused by PIK3CA somatic mutations. The umbrella term of "PIK3CA-related overgrowth spectrum (PROS)" was agreed upon. Key clinical diagnostic features and criteria for testing were proposed, and testing approaches were summarized. Preliminary recommendations for a uniform approach to assessment of overgrowth and molecular diagnostic testing were determined. Future areas to address including surgical management of overgrowth tissue and vascular anomalies, the optimal approach to thrombosis risk, and the testing of potential pharmacologic therapies. This paper introduced the outcomes of this workshop to provide clarity in research endeavors and to give clinicians useful designations for management, prognostication, and the design of clinical trials of targeted therapies.