Dynamic interplay between structural variations and 3D chromosome organization in pancreatic cancer
Dynamic interplay between structural variations and 3D chromosome organization in pancreatic cancer
Summary Structural variations (SVs) are the greatest source of variation in the genome and can lead to oncogenesis. However, the identification and interpretation of SVs in human pancreatic cancer remain largely undefined due to technological limitations. Here, we investigate the spectrum of SVs and three-dimensional (3D) chromatin architecture in human pancreatic ductal epithelial cell carcinogenesis by using state-of-the-art long- read single-molecule real-time (SMRT) and high-throughput chromosome conformation capture (Hi-C) sequencing techniques. We find that the 3D genome organization is remodeled and correlated with gene expressional change. The bulk remodeling effect of cross-boundary SVs in the 3D genome partly depends on intercellular genomic heterogeneity. Meanwhile, contact domains tend to minimize these disrupting effects of SVs within local adjacent genomic regions to maintain overall stability of 3D genome organization. Moreover, our data also demonstrates complex genomic rearrangements involving two key driver genes CDKN2A and SMAD4, and elucidates their influence on cancer-related gene expression from both linear view and 3D perspective. Overall, this study provides a valuable resource and highlights the impact, complexity and dynamicity of the interplay between SVs and 3D genome organization, which further expands our understanding of pathogenesis of SVs in human pancreatic cancer.
Wang Chengfeng、Li Zongze、Bo Xiaochen、Chen Hebing、Du Yongxing、Gu Zongting、Yuan Zan、Zheng Xiaohao、Zhao Yue
Department of Pancreatic and Gastric Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Pancreatic and Gastric Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Biotechnology, Beijing Institute of Radiation MedicineDepartment of Biotechnology, Beijing Institute of Radiation MedicineDepartment of Pancreatic and Gastric Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Pancreatic and Gastric Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeAnnoroad Gene Technology Co., LtdDepartment of Pancreatic and Gastric Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeAnnoroad Gene Technology Co., Ltd
肿瘤学基础医学分子生物学
Structural variations3D genomepancreatic cancerSMRTHi-C
Wang Chengfeng,Li Zongze,Bo Xiaochen,Chen Hebing,Du Yongxing,Gu Zongting,Yuan Zan,Zheng Xiaohao,Zhao Yue.Dynamic interplay between structural variations and 3D chromosome organization in pancreatic cancer[EB/OL].(2025-03-28)[2025-05-22].https://www.biorxiv.org/content/10.1101/2021.12.15.471847.点此复制
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