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Heterozygotic Brca1 mutation initiates mouse genome instability at embryonic stage
Wu, Xiaobing1; Guo, Maoni1; Cui, Jian2; Cai, Haoyang3; Wang, San Ming1
2022-12-01
Source PublicationOncogenesis
Volume11Issue:1
Abstract

BRCA1 mutation is the genetic predisposition in causing genome instability towards cancer. BRCA1 mutation is predominantly germline inherited at the fertilization. However, when the inherited mutation initiates genome instability in the mutation carriers remains largely elusive. We used a heterozygotic Brca1-knockout mouse as a model to investigate the issue. Through whole-genome sequencing and bioinformatics analysis, we monitored genome status across the developmental stages from embryo to adulthood in the mouse model. We observed that genome instability as reflected by structural variation, indel and copy number variation already appeared at 10.5-day embryo and progressively towards adulthood. We also observed that the genome instability was not linearly accumulated but dynamically changed along the developmental process, affecting many oncogenic genes and pathways including DNA damage repair, estrogen signaling, and oncogenesis. We further observed that many genome abnormalities in the cancer caused by Brca1 mutation were originated at embryonic stage, and Trp53 (TP53) mutation was not essential for the Brca1 mutation-caused genome instability in the non-cancer cells. Our study revealed that heterozygotic Brca1 mutation alone can cause genome instability at embryonic stage, highlighting that prevention of BRCA1 mutation-related cancer in humans may need to start earlier than currently considered.

DOI10.1038/s41389-022-00417-3
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaOncology
WOS SubjectOncology
WOS IDWOS:000829986700001
Scopus ID2-s2.0-85134599880
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Cited Times [WOS]:1   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Corresponding AuthorWang, San Ming
Affiliation1.MOE Frontiers Science Center for Precision Oncology, Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macao
2.Eppley Cancer Institute, University of Nebraska Medical Center, Omaha, United States
3.Center of Growth, Metabolism, and Aging, Key Laboratory of Bio-Resources and Eco-Environment, College of Life Sciences, Sichuan University, Chengdu, China
First Author AffilicationFaculty of Health Sciences
Corresponding Author AffilicationFaculty of Health Sciences
Recommended Citation
GB/T 7714
Wu, Xiaobing,Guo, Maoni,Cui, Jian,et al. Heterozygotic Brca1 mutation initiates mouse genome instability at embryonic stage[J]. Oncogenesis,2022,11(1).
APA Wu, Xiaobing,Guo, Maoni,Cui, Jian,Cai, Haoyang,&Wang, San Ming.(2022).Heterozygotic Brca1 mutation initiates mouse genome instability at embryonic stage.Oncogenesis,11(1).
MLA Wu, Xiaobing,et al."Heterozygotic Brca1 mutation initiates mouse genome instability at embryonic stage".Oncogenesis 11.1(2022).
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