Genetic landscape of common venous malformations in the head and neck
Genetic landscape of common venous malformations in the head and neck
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头颈部常见静脉畸形的遗传景观
DOI：
10.1016/j.jvsv.2020.11.016
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发表时间：
2021-06-15
影响因子：
3.2
通讯作者：
Wang, Yan-An
中科院分区：
文献类型：
--
作者：
Du, Zhong;Liu, Jia-Liang;Wang, Yan-An
目的：常见静脉畸形（VM）是一种常见的散发性血管畸形亚型。鉴于TEK和PIK 3CA突变的确定，本研究的目的是调查的遗传景观的VM在头部和颈部。方法：患者发表的测序研究相关的常见VM进行了审查。综合了关于临床特征、测序策略和突变频率的详细数据。结合上海市第九人民医院口腔颌面-头颈肿瘤科病理资料库，进一步回顾性分析头颈部常见VM的病变分布。对于头颈部的常见受累部位，选择患者进行设计的血管畸形相关基因组靶向测序或全外显子组测序。通过经典生物信息学算法（SIFT 23、PolyPhen-2 HDIV、LRT、MutationTaster、Mutation Assessor和GERPthornthorn）分析检测到的变体。为了确认特定候选基因的表达模式，对标本进行组织化学检查。结果：共检索到8篇与常见VM相关的测序研究中的300例患者。TEK和PIK 3CA突变的总患病率分别为41.3%和26.7%。最常见的TEK/PIK 3CA突变是TEK-L914 F/PIK 3CA-H1047 R。TEK/PIK 3CA突变在头颈部VM中的检出率分别为70.3%和2.7%。回顾性分析上海市第九医院649例颌面部VM患者的临床资料，发现颌面部（唇、颊、腮腺咬肌区、颌下区）和口腔口咽部（颊粘膜、舌）是最常见的VM部位。14个常见病变的靶向测序在3名患者（21.4%）中检测到TEK变异，但没有PIK 3CA突变。在两个没有TEK/PIK 3CA突变的患者的全外显子组测序中，CDH 11是唯一共有的有害突变基因。CDH 11的生物信息学分析表明，参与细胞粘附和连接的基因形成了显着的portion.Conclusions：常见的VM的头部和颈部有一个独特的遗传景观。新的CDH 11和TEK变体意味着发病机制是由内皮细胞和细胞外成分之间的调节关系介导的。
Objective: Common venous malformations (VMs) are a frequent sporadic subtype of vascular malformations. Given the TEK and PIK3CA mutations identified, this study aims to investigate the genetic landscape of VMs in the head and neck.Methods: Patients from published sequencing studies related to common VMs were reviewed. Detailed data regarding clinical characteristics, sequencing strategies, and mutation frequency were synthesized. Lesion distribution of common VMs in the head and neck were further retrospectively analyzed by the pathologic database of the Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital. For the frequently affected sites in the head and neck, patients were selected for targeted sequencing with a designed vascular malformation-related gene panel or whole exome sequencing. Detected variants were analyzed by classical bioinformatic algorithms (SIFT23, PolyPhen-2 HDIV, LRT, MutationTaster, Mutation Assessor, and GERPthornthorn). To confirm the expression pattern of particular candidate gene, specimens were examined histochemically. Gene ontology enrichment analysis and a protein-protein interaction network were also constructed.Results: Three hundred patients from eight sequencing studies related to common VMs were reviewed. The total prevalence rates of TEK and PIK3CA mutations were 41.3% and 26.7%, respectively. The most frequent TEK/PIK3CA mutations were TEK-L914F/PIK3CA-H1047R. TEK/PIK3CA mutations existed in 70.3% and 2.7% of VMs in the head and neck. In retrospective data from 649 patients carrying cervicofacial VMs at Shanghai Ninth Hospital, the most frequent sites were the maxillofacial region (lips, cheek, parotid-masseteric region, submandibular region) and the oral and oropharyngeal region (buccal mucosa, tongue). Targeted sequencing for 14 frequent lesions detected TEK variants in three patients (21.4%), but no PIK3CA mutations. On whole exome sequencing of two patients without TEK/PIK3CA mutations, CDH11 was the only shared deleteriously mutated gene. Bioinformatic analyses of CDH11 implied that genes involved in cellular adhesion and junctions formed a significant portion.Conclusions: Common VMs of the head and neck have a unique genetic landscape. Novel CDH11 and TEK variants imply that pathogenesis is mediated by the regulatory relationship between endothelial cells and extracellular components.