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Spatial and clonality-resolved 3D cancer genome alterations reveal enhancer-hijacking as a potential prognostic marker for colorectal cancer.
Kim, Kyukwang; Kim, Mooyoung; Lee, Andrew J; Song, Sang-Hyun; Kang, Jun-Kyu; Eom, Junghyun; Kang, Gyeong Hoon; Bae, Jeong Mo; Min, Sunwoo; Kim, Yeonsoo; Lim, Yoojoo; Kim, Han Sang; Kim, Young-Joon; Kim, Tae-You; Jung, Inkyung.
Afiliación
  • Kim K; Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Korea.
  • Kim M; Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Korea.
  • Lee AJ; Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Korea.
  • Song SH; Cancer Genomics Research Laboratory, Cancer Research Institute, Seoul National University, Seoul 03080, Korea; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 03080, Korea.
  • Kang JK; Cancer Genomics Research Laboratory, Cancer Research Institute, Seoul National University, Seoul 03080, Korea; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 03080, Korea.
  • Eom J; Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Korea.
  • Kang GH; Department of Pathology, Seoul National University Hospital, Seoul 03080, Korea.
  • Bae JM; Department of Pathology, Seoul National University Hospital, Seoul 03080, Korea.
  • Min S; Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Korea.
  • Kim Y; Cancer Genomics Research Laboratory, Cancer Research Institute, Seoul National University, Seoul 03080, Korea; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 03080, Korea.
  • Lim Y; Cancer Genomics Research Laboratory, Cancer Research Institute, Seoul National University, Seoul 03080, Korea; Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, Korea.
  • Kim HS; Yonsei Cancer Center, Division of Medical Oncology, Department of Internal Medicine, Graduate School of Medical Science, Brain Korea 21 Project, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul 03722, Korea.
  • Kim YJ; Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Korea.
  • Kim TY; Cancer Genomics Research Laboratory, Cancer Research Institute, Seoul National University, Seoul 03080, Korea; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 03080, Korea; Department of Internal
  • Jung I; Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Korea. Electronic address: ijung@kaist.ac.kr.
Cell Rep ; 42(7): 112778, 2023 07 25.
Article en En | MEDLINE | ID: mdl-37453058
ABSTRACT
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Colorrectales / Genoma Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Cell Rep Año: 2023 Tipo del documento: Article
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Colorrectales / Genoma Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Cell Rep Año: 2023 Tipo del documento: Article