한빛사논문
- 조회1,540
Eunhee Yi1, Amit D Gujar2, Molly Guthrie3, Hoon Kim4, Dacheng Zhao3, Kevin C. Johnson4, Samirkumar B Amin5, Megan L Costa6, Qianru Yu3, Sunit Das7, Nathaniel Jillette3, Patricia A Clow8, Albert W Cheng3 and Roel GW Verhaak3,*
1N.A., Jackson Laboratory for Genomic Medicine
2NA, The Jackson Laboratory for Genomic Medicine
3NA, Jackson Laboratory for Genomic Medicine
4Jackson Laboratory for Genomic Medicine
5Computational Cancer Biology, The Jackson Laboratory for Genomic Medicine
6Verhaak Lab, Jackson Laboratory for Genomic Medicine
7Division of Neurosurgery and Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto
8Albert Cheng Lab, Jackson Laboratory for Genomic Medicine
*Corresponding Author:Roel G Verhaak, NA, Jackson Laboratory for Genomic Medicine, Farmington, CT, 06032, United States.
Abstract
Oncogenic extrachromosomal DNA elements (ecDNAs) play an important role in tumor evolution, but our understanding of ecDNA biology is limited. We determined the distribution of single-cell ecDNA copy number across patient tissues and cell line models and observed how cell-to-cell ecDNA frequency greatly varies. The exceptional intratumoral heterogeneity of ecDNA suggested ecDNA-specific replication and propagation mechanisms. To evaluate the transfer of ecDNA genetic material from parental to offspring cells during mitosis, we established the CRISPR-based ecTag method. EcTag leverages ecDNA-specific breakpoint sequences to tag ecDNA with fluorescent markers in living cells. Applying ecTag during mitosis revealed disjointed ecDNA inheritance patterns, enabling rapid ecDNA accumulation in individual cells. Post-mitosis, ecDNAs clustered into ecDNA hubs, and ecDNA hubs colocalized with RNA polymerase II, promoting transcription of cargo oncogenes. Our observations provide direct evidence for uneven segregation of ecDNA and shed new light on mechanisms through which ecDNAs contribute to oncogenesis.
논문정보
- Research article
- 2021년 11월 (BRIC 등록일 2021-11-30)
- 국외 연구진
- 의약학 > 종양의학
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