In:
Frontiers in Cell and Developmental Biology, Frontiers Media SA, Vol. 9 ( 2021-7-23)
Abstract:
Human papillomavirus (HPV) integration is the major contributor to cervical cancer (CC) development by inducing structural variations (SVs) in the human genome. SVs are directly associated with the three-dimensional (3D) genome structure leading to cancer development. The detection of SVs is not a trivial task, and several genome-wide techniques have greatly helped in the identification of SVs in the cancerous genome. However, in cervical cancer, precise prediction of SVs mainly translocations and their effects on 3D-genome and gene expression still need to be explored. Here, we have used high-throughput chromosome conformation capture (Hi-C) data of cervical cancer to detect the SVs, especially the translocations, and validated it through whole-genome sequencing (WGS) data. We found that the cervical cancer 3D-genome architecture rearranges itself as compared to that in the normal tissue, and 24% of the total genome switches their A/B compartments. Moreover, translocation detection from Hi-C data showed the presence of high-resolution t (4;7) (q13.1; q31.32) and t (1;16) (q21.2; q22.1) translocations, which disrupted the expression of the genes located at and nearby positions. Enrichment analysis suggested that the disrupted genes were mainly involved in controlling cervical cancer-related pathways. In summary, we detect the novel SVs through Hi-C data and unfold the association among genome-reorganization, translocations, and gene expression regulation. The results help understand the underlying pathogenicity mechanism of SVs in cervical cancer development and identify the targeted therapeutics against cervical cancer.
Type of Medium:
Online Resource
ISSN:
2296-634X
DOI:
10.3389/fcell.2021.706375
DOI:
10.3389/fcell.2021.706375.s001
DOI:
10.3389/fcell.2021.706375.s002
DOI:
10.3389/fcell.2021.706375.s003
DOI:
10.3389/fcell.2021.706375.s004
DOI:
10.3389/fcell.2021.706375.s005
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2021
detail.hit.zdb_id:
2737824-X
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