Whole-Genome Sequencing Identifies a Novel Variation of WAS Gene Coordinating With Heterozygous Germline Mutation of APC to Enhance Hepatoblastoma Oncogenesis
机构：[1]Center for Bioinformatics and Computational Biology, and the Institute of Biomedical Sciences, School of Life Sciences, East China Normal University, Shanghai, China,[2]Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, MOE Key Laboratory of Major Diseases in Children, Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China,临床科室科研平台职能科室耳鼻咽喉头颈外科临床流行病与循证医学中心儿科研究所首都医科大学附属北京儿童医院[3]Biobank for Clinical Data and Samples in Pediatrics, Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China,科研平台职能科室临床流行病与循证医学中心儿科研究所首都医科大学附属北京儿童医院[4]Department of General Surgery, Wuhan Children’s Hospital, Wuhan, China,[5]Department of Surgery, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China,临床科室职能科室急症普外科临床流行病与循证医学中心首都医科大学附属北京儿童医院[6]Department of Otolaryngology, Head and Neck Surgery, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China临床科室职能科室耳鼻咽喉头颈外科临床流行病与循证医学中心首都医科大学附属北京儿童医院
Hepatoblastoma (HB), a leading primary hepatic malignancy in children, originates from primitive hepatic stem cells. This study aimed to uncover the genetic variants that are responsible for HB oncogenesis. One family, which includes the healthy parents, and two brothers affected by HB, was recruited. Whole-genome sequencing (WGS) of germline DNA from all the family members identified two maternal variants, located within APC gene and X-linked WAS gene, which were harbored by the two brothers. The mutation of APC (rs137854573, c.C1606T, p.R536X) could result in HB carcinogenesis by activating Wnt signaling. The WAS variant (c.G3T, p.M1-P5del) could promote HB cell proliferation and inhibit T-cell-based immunity by activating PLK1 signaling and inactivating TCR signaling. Further analysis reflected that WAS deficiency might affect the antitumor activity of natural killer and dendritic cells. In summary, the obtained results imply that an APC mutant together with an X-linked WAS mutant, could lead to HB tumorigenesis by activating Wnt and PLK1 signaling, inhibiting TCR signaling, and reducing the antitumor activity of natural killer and dendritic cells.
基金：
National High Technology Research and Development Program of ChinaNational High Technology Research and Development Program of China [2015AA020108]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81472369, 31671377, 81502144]; Shanghai 111 project; Beijing Health System Top Level Health Technical Personnel Training Plan [20153079]
第一作者机构：[1]Center for Bioinformatics and Computational Biology, and the Institute of Biomedical Sciences, School of Life Sciences, East China Normal University, Shanghai, China,
共同第一作者：
通讯作者：
通讯机构：[1]Center for Bioinformatics and Computational Biology, and the Institute of Biomedical Sciences, School of Life Sciences, East China Normal University, Shanghai, China,[2]Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, MOE Key Laboratory of Major Diseases in Children, Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China,[3]Biobank for Clinical Data and Samples in Pediatrics, Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China,[6]Department of Otolaryngology, Head and Neck Surgery, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China
推荐引用方式(GB/T 7714)：
Li Zhang,Yaqiong Jin,Kai Zheng,et al.Whole-Genome Sequencing Identifies a Novel Variation of WAS Gene Coordinating With Heterozygous Germline Mutation of APC to Enhance Hepatoblastoma Oncogenesis[J].FRONTIERS IN GENETICS.2018,9:-.doi:10.3389/fgene.2018.00668.
APA：
Li Zhang,Yaqiong Jin,Kai Zheng,Huanmin Wang,Shen Yang...&Xin Ni.(2018).Whole-Genome Sequencing Identifies a Novel Variation of WAS Gene Coordinating With Heterozygous Germline Mutation of APC to Enhance Hepatoblastoma Oncogenesis.FRONTIERS IN GENETICS,9,
MLA：
Li Zhang,et al."Whole-Genome Sequencing Identifies a Novel Variation of WAS Gene Coordinating With Heterozygous Germline Mutation of APC to Enhance Hepatoblastoma Oncogenesis".FRONTIERS IN GENETICS 9.(2018):-
