Frontiers in Genetics (Jul 2021)
A Novel Germline Compound Heterozygous Mutation of BRCA2 Gene Associated With Familial Peripheral Neuroblastic Tumors in Two Siblings
- Yeran Yang,
- Yeran Yang,
- Yeran Yang,
- Jiwei Chen,
- Hong Qin,
- Yaqiong Jin,
- Yaqiong Jin,
- Yaqiong Jin,
- Li Zhang,
- Shen Yang,
- Huanmin Wang,
- Libing Fu,
- Enyu Hong,
- Enyu Hong,
- Yongbo Yu,
- Yongbo Yu,
- Yongbo Yu,
- Jie Lu,
- Jie Lu,
- Jie Lu,
- Yan Chang,
- Yan Chang,
- Yan Chang,
- Xin Ni,
- Xin Ni,
- Xin Ni,
- Min Xu,
- Tieliu Shi,
- Yongli Guo,
- Yongli Guo,
- Yongli Guo
Affiliations
- Yeran Yang
- Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, MOE Key Laboratory of Major Diseases in Children, National Center for Children’s Health, Beijing Children’s Hospital, Beijing Pediatric Research Institute, Capital Medical University, Beijing, China
- Yeran Yang
- Biobank for Clinical Data and Samples in Pediatric, National Center for Children’s Health, Beijing Children’s Hospital, Beijing Pediatric Research Institute, Capital Medical University, Beijing, China
- Yeran Yang
- Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University, Capital Medical University, Beijing, China
- Jiwei Chen
- Center for Bioinformatics and Computational Biology, School of Life Sciences, Institute of Biomedical Sciences, East China Normal University, Shanghai, China
- Hong Qin
- Department of Surgical Oncology, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, China
- Yaqiong Jin
- Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, MOE Key Laboratory of Major Diseases in Children, National Center for Children’s Health, Beijing Children’s Hospital, Beijing Pediatric Research Institute, Capital Medical University, Beijing, China
- Yaqiong Jin
- Biobank for Clinical Data and Samples in Pediatric, National Center for Children’s Health, Beijing Children’s Hospital, Beijing Pediatric Research Institute, Capital Medical University, Beijing, China
- Yaqiong Jin
- Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University, Capital Medical University, Beijing, China
- Li Zhang
- Center for Bioinformatics and Computational Biology, School of Life Sciences, Institute of Biomedical Sciences, East China Normal University, Shanghai, China
- Shen Yang
- Department of Surgical Oncology, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, China
- Huanmin Wang
- Department of Surgical Oncology, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, China
- Libing Fu
- Department of Pathology, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, China
- Enyu Hong
- Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, MOE Key Laboratory of Major Diseases in Children, National Center for Children’s Health, Beijing Children’s Hospital, Beijing Pediatric Research Institute, Capital Medical University, Beijing, China
- Enyu Hong
- Biobank for Clinical Data and Samples in Pediatric, National Center for Children’s Health, Beijing Children’s Hospital, Beijing Pediatric Research Institute, Capital Medical University, Beijing, China
- Yongbo Yu
- Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, MOE Key Laboratory of Major Diseases in Children, National Center for Children’s Health, Beijing Children’s Hospital, Beijing Pediatric Research Institute, Capital Medical University, Beijing, China
- Yongbo Yu
- Biobank for Clinical Data and Samples in Pediatric, National Center for Children’s Health, Beijing Children’s Hospital, Beijing Pediatric Research Institute, Capital Medical University, Beijing, China
- Yongbo Yu
- Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University, Capital Medical University, Beijing, China
- Jie Lu
- Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, MOE Key Laboratory of Major Diseases in Children, National Center for Children’s Health, Beijing Children’s Hospital, Beijing Pediatric Research Institute, Capital Medical University, Beijing, China
- Jie Lu
- Biobank for Clinical Data and Samples in Pediatric, National Center for Children’s Health, Beijing Children’s Hospital, Beijing Pediatric Research Institute, Capital Medical University, Beijing, China
- Jie Lu
- Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University, Capital Medical University, Beijing, China
- Yan Chang
- Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, MOE Key Laboratory of Major Diseases in Children, National Center for Children’s Health, Beijing Children’s Hospital, Beijing Pediatric Research Institute, Capital Medical University, Beijing, China
- Yan Chang
- Biobank for Clinical Data and Samples in Pediatric, National Center for Children’s Health, Beijing Children’s Hospital, Beijing Pediatric Research Institute, Capital Medical University, Beijing, China
- Yan Chang
- Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University, Capital Medical University, Beijing, China
- Xin Ni
- Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, MOE Key Laboratory of Major Diseases in Children, National Center for Children’s Health, Beijing Children’s Hospital, Beijing Pediatric Research Institute, Capital Medical University, Beijing, China
- Xin Ni
- Biobank for Clinical Data and Samples in Pediatric, National Center for Children’s Health, Beijing Children’s Hospital, Beijing Pediatric Research Institute, Capital Medical University, Beijing, China
- Xin Ni
- Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University, Capital Medical University, Beijing, China
- Min Xu
- Department of Surgery, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- Tieliu Shi
- Center for Bioinformatics and Computational Biology, School of Life Sciences, Institute of Biomedical Sciences, East China Normal University, Shanghai, China
- Yongli Guo
- Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, MOE Key Laboratory of Major Diseases in Children, National Center for Children’s Health, Beijing Children’s Hospital, Beijing Pediatric Research Institute, Capital Medical University, Beijing, China
- Yongli Guo
- Biobank for Clinical Data and Samples in Pediatric, National Center for Children’s Health, Beijing Children’s Hospital, Beijing Pediatric Research Institute, Capital Medical University, Beijing, China
- Yongli Guo
- Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University, Capital Medical University, Beijing, China
- DOI
- https://doi.org/10.3389/fgene.2021.652718
- Journal volume & issue
-
Vol. 12
Abstract
ObjectivesTo investigate the genetic variants that are responsible for peripheral neuroblastic tumors (PNTs) oncogenesis in one family case.Materials and MethodsOne family was recruited, including the healthy parents, sister affected by neuroblastoma (NB), and brother who suffered from ganglioneuroma (GN). Whole-genome sequencing (WGS) of germline DNA from all the family members and RNA-seq of tumor RNA from the siblings were performed. Mutants were validated by Sanger sequencing and co-IP was performed to assess the impact of the mutant on chemosensitivity in the SH-SY5Y cell line.ResultsA novel compound heterozygous mutation of BRCA2 was locked as the cause of carcinogenesis. One allele was BRCA2-S871X (stop-gain) from the siblings’ mother, the other was BRCA2-N372H (missense) from their father. This novel compound heterozygous mutations of the BRCA2 gene associated with PNTs by disordering DNA damage and response (DDR) signal pathway. Moreover, chemosensitivity was reduced in the NB cell line due to the BRCA2-N372H mutant.ConclusionIn summary, these results revealed a novel germline compound heterozygous mutation of the BRCA2 gene associated with familial PNTs.
Keywords
