Dynamic Interplay between Structural Variations and 3D Genome Organization in Pancreatic Cancer
Abstract: Structural variations (SVs) are the greatest source of variations in the genome and can lead to oncogenesis. However, the identification and interpretation of SVs in human cancer remain technologically challenging. Here, long‐read sequencing is first employed to depict the signatures of structural variations in carcinogenesis of human pancreatic ductal epithelium. Then widespread reprogramming of the 3D chromatin architecture is revealed by an in situ Hi‐C technique. Integrative analyses indicate that the distribution pattern of SVs among the 3D genome is highly cell‐type specific and the bulk remodeling effects of SVs in the chromatin organization partly depend on intercellular genomic heterogeneity. Meanwhile, contact domains tend to minimize these disrupting effects of SVs within local adjacent genomic regions to maintain overall stability. Notably, complex genomic rearrangements involving two key driver genes CDKN2A and SMAD4 are identified, and their influence on the expression of oncogenes MIR31HG, MYO5B, etc., are further elucidated from both a linear view and 3D perspective. Overall, this work provides a genome‐wide resource and highlights the impact, complexity, and dynamicity of the interplay between structural variations and high‐order chromatin organization, which expands the current understanding of the pathogenesis of SVs in human cancer.
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Bibliographic citation
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Dynamic Interplay between Structural Variations and 3D Genome Organization in Pancreatic Cancer ; day:15 ; month:05 ; year:2022 ; extent:19
Advanced science ; (15.05.2022) (gesamt 19)
- Creator
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Du, Yongxing
Gu, Zongting
Li, Zongze
Yuan, Zan
Zhao, Yue
Zheng, Xiaohao
Bo, Xiaochen
Chen, Hebing
Wang, Chengfeng
- DOI
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10.1002/advs.202200818
- URN
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urn:nbn:de:101:1-2022051615061910141247
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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15.08.2025, 7:36 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Du, Yongxing
- Gu, Zongting
- Li, Zongze
- Yuan, Zan
- Zhao, Yue
- Zheng, Xiaohao
- Bo, Xiaochen
- Chen, Hebing
- Wang, Chengfeng
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