Oncogenic extrachromosomal DNA functions as mobile enhancers to globally amplify chromosomal transcription
| Autor: | Meihong Li, Liang Gong, Yanfen Zhu, Chris Kuhlberg, Jihe Liu, Adam Mil-Homens, Ana C. deCarvalho, Chia-Lin Wei, Roel G.W. Verhaak, Yi-An Chen, Chew Yee Ngan, Yijun Ruan, Chee Hong Wong, Rahul Maurya, Eun Hee Yi, Harianto Tjong, Fanyue Sun, Amit D. Gujar, Hoon Kim |
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| Přispěvatelé: | Neurosurgery |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cancer Research Carcinogenesis Biology Chromosomes 03 medical and health sciences 0302 clinical medicine Transcription (biology) Extrachromosomal DNA medicine Humans Enhancer Gene ChIA-PET Cancer DNA Neoplasm Oncogenes medicine.disease Chromatin Cell biology 030104 developmental biology Oncology Tumor progression 030220 oncology & carcinogenesis Glioblastoma |
| Zdroj: | Cancer Cell, 39(5), 694-707.e7. Cell Press Zhu, Y, Gujar, A D, Wong, C-H, Tjong, H, Ngan, C Y, Gong, L, Chen, Y-A, Kim, H, Liu, J, Li, M, Mil-Homens, A, Maurya, R, Kuhlberg, C, Sun, F, Yi, E, deCarvalho, A C, Ruan, Y, Verhaak, R G W & Wei, C-L 2021, ' Oncogenic extrachromosomal DNA functions as mobile enhancers to globally amplify chromosomal transcription ', Cancer Cell, vol. 39, no. 5, pp. 694-707.e7 . https://doi.org/10.1016/j.ccell.2021.03.006 |
| ISSN: | 1535-6108 |
| DOI: | 10.1016/j.ccell.2021.03.006 |
| Popis: | Extrachromosomal, circular DNA (ecDNA) is emerging as a prevalent yet less characterized oncogenic alteration in cancer genomes. We leverage ChIA-PET and ChIA-Drop chromatin interaction assays to characterize genome-wide ecDNA-mediated chromatin contacts that impact transcriptional programs in cancers. ecDNAs in glioblastoma patient-derived neurosphere and prostate cancer cell cultures are marked by widespread intra-ecDNA and genome-wide chromosomal interactions. ecDNA-chromatin contact foci are characterized by broad and high-level H3K27ac signals converging predominantly on chromosomal genes of increased expression levels. Prostate cancer cells harboring synthetic ecDNA circles composed of characterized enhancers result in the genome-wide activation of chromosomal gene transcription. Deciphering the chromosomal targets of ecDNAs at single-molecule resolution reveals an association with actively expressed oncogenes spatially clustered within ecDNA-directed interaction networks. Our results suggest that ecDNA can function as mobile transcriptional enhancers to promote tumor progression and manifest a potential synthetic aneuploidy mechanism of transcription control in cancer. |
| Databáze: | OpenAIRE |
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