| Literature DB >> 36272974 |
Heyang Cui1,2, Yong Zhou1,3, Fang Wang2, Caixia Cheng4, Weimin Zhang1,5,6, Ruifang Sun7, Ling Zhang2, Yanghui Bi2, Min Guo2, Yan Zhou2, Xinhui Wang2, Jiaxin Ren4, Ruibing Bai4, Ning Ding1, Chen Cheng1, Longlong Wang1, Xuehan Zhuang1, Mingwei Gao1, Yongjia Weng1, Yueguang Wu1, Huijuan Liu2, Shuaicheng Li3, Shubin Wang8, Xiaolong Cheng2, Yongping Cui9,10, Zhihua Liu11, Qimin Zhan12,13,14.
Abstract
Esophageal squamous cell carcinoma (ESCC) demonstrates high genome instability. Here, we analyze 528 whole genomes to investigate structural variations' mechanisms and biological functions. SVs show multi-mode distributions in size, indicating distinct mutational processes. We develop a tool and define five types of complex rearrangements with templated insertions. We highlight a type of fold-back inversion, which is associated with poor outcomes. Distinct rearrangement signatures demonstrate variable genomic metrics such as replicating time, spatial proximity, and chromatin accessibility. Specifically, fold-back inversion tends to occur near the centrosome; TD-c2 (Tandem duplication-cluster2) is significantly enriched in chromatin-accessibility and early-replication region compared to other signatures. Analyses of TD-c2 signature reveal 9 TD hotspots, of which we identify a hotspot consisting of a super-enhancer of PTHLH. We confirm the oncogenic effect of the PTHLH gene and its interaction with enhancers through functional experiments. Finally, extrachromosomal circular DNAs (ecDNAs) are present in 14% of ESCCs and have strong selective advantages to driver genes.Entities:
Year: 2022 PMID： 36272974 DOI： 10.1038/s41467-022-33994-3
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 17.694