| 项目编号 | PRJCA013314 | |||||||||||||||
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| 项目标题 | Extrachromosomal Circular DNA Orchestrates Genome Heterogeneity and Outcome in Urothelial Bladder Carcinoma | |||||||||||||||
| 涉及领域 | Medical | |||||||||||||||
| 数据类型 |
Whole genome sequencing
Exome Transcriptome or Gene expression Raw sequence reads Genome sequencing |
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| 物种名称 | Homo sapiens | |||||||||||||||
| 描述信息 | Extrachromosomal circular DNA is a newly evolved hallmark in cancer and is associated with cancer genome instability, oncogene amplification, acquired resistance, and disease progression. A Cancer Circular Genome Atlas (CCGA) consortium is formed to map the missing link of circulome in cancers. Here, we report our pilot CCGA results which we comprehensively characterize the chromosomal DNA, extrachromosomal circular DNA, and transcriptomic alteration landscape in urothelial bladder carcinoma (UBC) of 80 patients by whole-genome/exon sequencing, Circle-seq, single-molecule long-read sequencing technology, and RNA sequencing. Leveraging these large amounts of pair-wise (UBC vs. normal adjacent tissue) and trans-OMICS (genome, circulome, transcriptome) data, we exploit the genome-wide landscape of circular DNA-associated somatic mutations, unbalanced structural variations, oncogene amplification, genomic distributions, structure, and correlations with altered gene expression and clinical outcomes in UBCs. Our results reveal that UBCs contain high load of extrachromosomal circular DNAs which are in cis correlated with cluster of hypermutations (kataegis), copy number variations, oncogene amplifications, structure variations, DNA repair alteration, as well as poor clinical survival. Furthermore, our analyses probe high frequency (81%) of chromothripsis-like events in UBCs, supported by the detection of an extremely chimeric circular DNA containing DNA fragments from nine chromosomes. The CCGA-UBC presents an integrative trans-OMICS analysis strategy to map landscape of extrachromosomal circular DNAs in cancers and may provide opportunities for the development of novel therapeutic strategies. | |||||||||||||||
| 样品范围 | Multiisolate | |||||||||||||||
| 发布日期 | 2023-02-28 | |||||||||||||||
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| 提交者 | Hanbo Li (lihanbo@genomics.cn) | |||||||||||||||
| 提交单位 | BGI | |||||||||||||||
| 提交日期 | 2022-11-18 |
| 资源名称 | 描述 |
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| BioSample (698) show | - |