AUTHOR=Adeel Muhammad Muzammal , Jiang Hao , Arega Yibeltal , Cao Kai , Lin Da , Cao Canhui , Cao Gang , Wu Peng , Li Guoliang TITLE=Structural Variations of the 3D Genome Architecture in Cervical Cancer Development JOURNAL=Frontiers in Cell and Developmental Biology VOLUME=Volume 9 - 2021 YEAR=2021 URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.706375 DOI=10.3389/fcell.2021.706375 ISSN=2296-634X ABSTRACT=Human papillomavirus (HPV) integration is the major contributor to cervical cancer development by inducing structural variations (SVs) in the human genome. Structural Variations (SVs) are directly associated with the three-dimensional 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 three-dimensional (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 structural variations, 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, translocations detection from Hi-C data showed the presence of high-resolution t(4;7)(q13.1;q31.3) and t(1;16)(q21.2;q22.1) translocations, which disrupted the expression of the genes located at and nearby positions. Enrichment analysis suggested 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 structural variations in cervical cancer development and identify the targeted therapeutics against cervical cancer.