期刊
CANCER CELL
卷 39, 期 5, 页码 694-+出版社
CELL PRESS
DOI: 10.1016/j.ccell.2021.03.006
关键词
-
资金
- 4DN consortia [U54 DK107967]
- ENCODE consortia [UM1 HG009409]
- NCI [P30CA034196]
- US National Institutes of Health [R01 GM127531, R33 CA236681, R01 CA190121, R01 CA237208, R21 NS114873]
- Musella Foundation
- B*CURED Foundation
- Brain Tumour Charity
- Department of Defense [W81XWH1910246]
- U.S. Department of Defense (DOD) [W81XWH1910246] Funding Source: U.S. Department of Defense (DOD)
The study reveals that extrachromosomal, circular DNA (ecDNA) is a common and oncogenic alteration in cancer genomes, impacting transcriptional programs through chromatin interactions. ecDNAs in neurosphere and prostate cancer cell cultures show widespread intra-ecDNA and genome-wide chromosomal interactions, potentially leading to high-level expression of chromosomal genes.
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据