Optical Genome Mapping Reveals the Landscape of Structural Variations and Their Clinical Significance in HBOC-Related Breast Cancer

doi:10.31083/j.fbl2901002

	Optical Genome Mapping Reveals the Landscape of Structural Variations and Their Clinical Significance in HBOC-Related Breast Cancer
	Cheng, Yanan 1,2; Dong, Li 1,2; Bu, Dechao 3; Han, Lei 1,2; Zhao, Yi 3; Liu, Juntian 4; Guo, Xiaojing 5; Xu, Hanli 6; Yu, Jinpu 1,2
	2024
发表期刊	FRONTIERS IN BIOSCIENCE-LANDMARK
ISSN	2768-6701
卷号	29 期号:1 页码:1-15
摘要	Background: Structural variations (SVs) are common genetic alterations in the human genome. However, the profile and clinical relevance of SVs in patients with hereditary breast and ovarian cancer (HBOC) syndrome (germline BRCA1/2 mutations) remains to be fully elucidated. Methods: Twenty HBOC-related cancer samples (5 breast and 15 ovarian cancers) were studied by optical genome mapping (OGM) and next-generation sequencing (NGS) assays. Results: The SV landscape in the 5 HBOC-related breast cancer samples was comprehensively investigated to determine the impact of intratumor SV heterogeneity on clinicopathological features and on the pattern of genetic alteration. SVs and copy number variations (CNVs) were common genetic events in HBOC-related breast cancer, with a median of 212 SVs and 107 CNVs per sample. The most frequently detected type of SV was insertion, followed by deletion. The 5 HBOC-related breast cancer samples were divided into SVhigh and SVlow groups according to the intratumor heterogeneity of SVs. SVhigh tumors were associated with higher Ki-67 expression, higher homologous recombination deficiency (HRD) scores, more mutated genes, and altered signaling pathways. Moreover, 60% of the HBOC-related breast cancer samples displayed chromothripsis, and 8 novel gene fusion events were identified by OGM and validated by transcriptome data. Conclusions: These findings suggest that OGM is a promising tool for the detection of SVs and CNVs in HBOC-related breast cancer. Furthermore, OGM can efficiently characterize chromothripsis events and novel gene fusions. SVhigh HBOC-related breast cancers were associated with unfavorable clinicopathological features. SVs may therefore have predictive and therapeutic significance for HBOC-related breast cancers in the clinic.
关键词	HBOC breast cancer optical genome mapping structural variation BRCA1/2 chromothripsis
DOI	10.31083/j.fbl2901002
收录类别	SCI
语种	英语
资助项目	dation of China[82072588] ; dation of China[82002601] ; dation of China[81872143] ; dation of China[81702280] ; Projects of Science and Tech-nology of Tianjin[18JCQNJC82700] ; Tianjin Key Medical Discipline (Specialty) Construction Project[TJYXZDXK-009A]
WOS研究方向	Biochemistry & Molecular Biology ; Cell Biology
WOS类目	Biochemistry & Molecular Biology ; Cell Biology
WOS记录号	WOS:001155765700004
出版者	IMR PRESS
引用统计	被引频次：2[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://119.78.100.204/handle/2XEOYT63/38382
专题	中国科学院计算技术研究所期刊论文_英文
通讯作者	Xu, Hanli; Yu, Jinpu
作者单位	1.Tianjin Med Univ Canc Inst & Hosp, Natl Clin Res Ctr Canc, Tianjins Clin Res Ctr Canc, Canc Mol Diagnost Core, Tianjin 300060, Peoples R China 2.Tianjin Med Univ, Key Lab Canc Prevent & Therapy, Key Lab Canc Immunol & Biotherapy, Key Lab Breast Canc Prevent & Therapy,Minist Educ, Tianjin 300060, Peoples R China 3.Chinese Acad Sci, Res Ctr Ubiquitous Comp Syst, Inst Comp Technol, Beijing 100190, Peoples R China 4.Tianjin Med Univ Canc Inst & Hosp, Canc Prevent Ctr, Natl Clin Res Ctr Canc, Tianjins Clin Res Ctr Canc,Dept Breast Canc 2, Tianjin 300060, Peoples R China 5.Tianjin Med Univ Canc Inst & Hosp, Dept Breast Pathol & Lab, Natl Clin Res Ctr Canc, Tianjins Clin Res Ctr Canc, Tianjin 300060, Peoples R China 6.Beijing Jiaotong Univ, Coll Life Sci & Bioengn, Sch Phys Sci & Engn, Beijing 100044, Peoples R China
推荐引用方式 GB/T 7714	Cheng, Yanan,Dong, Li,Bu, Dechao,et al. Optical Genome Mapping Reveals the Landscape of Structural Variations and Their Clinical Significance in HBOC-Related Breast Cancer[J]. FRONTIERS IN BIOSCIENCE-LANDMARK,2024,29(1):1-15.
APA	Cheng, Yanan.,Dong, Li.,Bu, Dechao.,Han, Lei.,Zhao, Yi.,...&Yu, Jinpu.(2024).Optical Genome Mapping Reveals the Landscape of Structural Variations and Their Clinical Significance in HBOC-Related Breast Cancer.FRONTIERS IN BIOSCIENCE-LANDMARK,29(1),1-15.
MLA	Cheng, Yanan,et al."Optical Genome Mapping Reveals the Landscape of Structural Variations and Their Clinical Significance in HBOC-Related Breast Cancer".FRONTIERS IN BIOSCIENCE-LANDMARK 29.1(2024):1-15.