Somatic mutation spectrum of a Chinese cohort of pediatrics with vascular malformations

作者：Bin Zhang, Rui He, Zigang Xu, Yujuan Sun, Wei Li, Li Li, Yuanxiang Liu, Wu Guo, Li Song, Huijun Wang, Zhimiao Lin, Lin Ma · 发表于：Orphanet Journal of Rare Diseases · 年份：2023 · DOI：10.1186/s13023-023-02860-w · 被引用次数：12 · 研究领域：Vascular Malformations and Hemangiomas、Soft tissue tumors and treatment、Tumors and Oncological Cases

BACKGROUND: Somatic mutations of cancer driver genes are found to be responsible for vascular malformations with clinical manifestations ranging from cutaneous birthmarks to life-threatening systemic anomalies. Till now, only a limited number of cases and mutations were reported in Chinese population. The purpose of this study was to describe the somatic mutation spectrum of a cohort of Chinese pediatrics with vascular malformations. METHODS: Pediatrics diagnosed with various vascular malformations were collected between May 2019 and October 2020 from Beijing Children's Hospital. Genomic DNA of skin lesion of each patient was extracted and sequenced by whole-exome sequencing to identify pathogenic somatic mutations. Mutations with variant allele frequency less than 5% were validated by ultra-deep sequencing. RESULTS: A total of 67 pediatrics (33 males, 34 females, age range: 0.1-14.8 years) were analyzed. Exome sequencing identified somatic mutations of corresponding genes in 53 patients, yielding a molecular diagnosis rate of 79.1%. Among 29 PIK3CA mutations, 17 were well-known hotspot p.E542K, p.E545K and p.H1047R/L. Non-hotspot mutations were prevalent in patients with PIK3CA-related overgrowth spectrum, accounting for 50.0% (11/22) of detected mutations. The hotspot GNAQ p.R183Q and TEK p.L914F mutations were responsible for the majority of port-wine stain/Sturge-Weber syndrome and venous malformation, respectively. In addition, we identified a novel AKT1 p.Q79K mutation ...