| Autor: |
Wei Lv, Xiaoguang Pan, Peng Han, Shuang Wu, Yuchen Zeng, Qingqing Wang, Lidong Guo, Mengyang Xu, Fei Wang, Zhe Xu, Yi Li, Huajing Teng, Conghui Li, Kairu Qi, Shang Gao, Tianxi Yu, Xin Cui, Chongjun Xiang, Yue Li, Haotian Tan, Ning Liang, Huiying Tao, Guohua Yu, Jia Mi, Fuyi Xu, Benjiao Gong, Lei Shi, Tao Wang, Lars Bolund, Huan-Ming Yang, Wenting Wang, Hanbo Li, Jinrong Huang, Chunhua Lin, Yonglun Luo |
| Rok vydání: |
2023 |
| DOI: |
10.21203/rs.3.rs-2169951/v1 |
| Popis: |
Extrachromosomal circular DNA (circulome) is a newly evolved hallmark in cancer whereas its role in shaping the cancer genome heterogeneity is yet to be sufficiently understood. Here, we comprehensively characterize and exploit the circulome-associated genome heterogeneity in 80 urothelial bladder carcinoma (UBC) patients by whole-genome/exome sequencing, Circle-Seq, long-read sequencing, and RNA-seq. Our results reveal a high load and heterogeneity of UBC circulome. Many single locus and chimeric circular DNAs originating from different chromosomes are identified, including extremely chimeric circular DNAs carrying seven oncogenes and circles from nine chromosomes. Circular DNAs contribute to increased oncogene dosage and could influence genome-wide gene expression. Increased expression of DNA repair genes (LIG3, POLQ, BRCA1, and BRCA2) promote circulome generation in UBCs. The circulome is in cis correlated with hypermutation (kataegis), copy number variation, oncogene amplification, structure variation, and poor clinical outcome. These results strongly support circulome associations with UBC genome heterogeneity, progression, and outcome. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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