| Autor: |
Kyukwang Kim, Mooyoung Kim, Andrew J. Lee, Sang-Hyun Song, Jun-Kyu Kang, Junghyun Eom, Gyeong Hoon Kang, Jeong Mo Bae, Sunwoo Min, Yeonsoo Kim, Yoojoo Lim, Han Sang Kim, Young-Joon Kim, Tae-You Kim, Inkyung Jung |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Cell Reports, Vol 42, Iss 7, Pp 112778- (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2023.112778 |
| Popis: |
Summary: The regulatory effect of non-coding large-scale structural variations (SVs) on proto-oncogene activation remains unclear. This study investigated SV-mediated gene dysregulation by profiling 3D cancer genome maps from 40 patients with colorectal cancer (CRC). We developed a machine learning-based method for spatial characterization of the altered 3D cancer genome. This revealed a frequent establishment of “de novo chromatin contacts” that can span multiple topologically associating domains (TADs) in addition to the canonical TAD fusion/shuffle model. Using this information, we precisely identified super-enhancer (SE)-hijacking and its clonal characteristics. Clonal SE-hijacking genes, such as TOP2B, are recurrently associated with cell-cycle/DNA-processing functions, which can potentially be used as CRC prognostic markers. Oncogene activation and increased drug resistance due to SE-hijacking were validated by reconstructing the patient’s SV using CRISPR-Cas9. Collectively, the spatial and clonality-resolved analysis of the 3D cancer genome reveals regulatory principles of large-scale SVs in oncogene activation and their clinical implications. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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