이혜림 (Stanford University School of Medicine) | 한빛사논문 > 한빛사

한빛사논문

조회569

Stanford University School of Medicine

CV File

Cell, January 07, 2026 | https://doi.org/10.1016/j.cell.2025.12.009 EcDNA-borne structural variants drive oncogenic fusion transcript amplification

Hyerim Yi,^1,2,3,4,18 Shu Zhang,^1,2,3,4,18 Jason Swinderman,^5,6 Yanbo Wang,^1,2,3,4 Vishnupriya Kanakaveti,^3,7 King L. Hung,^2,16 Ivy Tsz-Lo Wong,^3,4 Suhas Srinivasan,^1,2Ellis J. Curtis,^3,4,8 Aarohi Bhargava-Shah,^1,2,9Rui Li,^1,2 Matthew G. Jones,^1,2 Jens Luebeck,¹⁰ Chris Bailey,¹¹ Yanding Zhao,^1,2Julia A. Belk,^1,2 Katerina Kraft,^1,2,17 Quanming Shi,^1,2,17 Xiaowei Yan,^1,2,3,4Simon K. Pritchard,¹ Kabir S. Mahajan,¹ Frances Liang,¹ Mariam Jamal-Hanjani,^12,13,14Dean W. Felsher,^3,7 Luke A. Gilbert,^5,6Vineet Bafna,^10,15Paul S. Mischel,^3,4,* and Howard Y. Chang ^1,2,17,19,*

¹RNA Medicine Program, Stanford University, Stanford, CA, USA
²Departments of Dermatology and Genetics, Stanford University School of Medicine, Stanford, CA, USA
³Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA
⁴Sarafan ChEM-H, Stanford University, Stanford, CA, USA
⁵Arc Institute, Palo Alto, CA, USA
⁶Department of Urology, University of California, San Francisco, San Francisco, CA, USA
⁷Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
⁸School of Medicine, University of California at San Diego, La Jolla, CA, USA
⁹School of Medicine, Stanford University, Stanford, CA, USA

¹⁰Department of Computer Science and Engineering, University of California at San Diego, La Jolla, CA, USA
¹¹Cancer Evolution and Genome Instability Laboratory, the Francis Crick Institute, London, UK
¹²Cancer Metastasis Laboratory, University College London Cancer Institute, London, UK
¹³Cancer Research UK Lung Cancer Centre of Excellence, UCL Cancer Institute, London, UK
¹⁴Department of Medical Oncology, University College London Hospitals, London, UK
¹⁵Halıcıoglu Data Science Institute, University of California at San Diego, La Jolla, CA, USA
¹⁶Present address: Department of Neuroscience, Scripps Research, La Jolla, CA, USA
¹⁷Present address: Amgen Research, South San Francisco, CA, USA

¹⁸These authors contributed equally
¹⁹Lead contact

^*Corresponding authors: correspondence to Paul S. Mischel or Howard Y. Chang

Abstract

Extrachromosomal DNA (ecDNA) amplifications are key drivers of human cancers. Here, we show that ecDNAs are major platforms for generating and amplifying oncogene fusion transcripts across diverse cancer types. By integrating analysis of whole-genome and transcriptome sequences from tumor samples and cancer cell lines of a wide variety of tissue types, we reveal that ecDNAs have the highest rate of oncogene fusion events of any copy-number alteration. Focusing on the most common ecDNA fusion hotspot, we find that fusion of the 5′ end of the long noncoding RNA gene, PVT1—with exon 1 joined to diverse 3′ partners—confers increased RNA stability, potentially via an SRSF1-dependent mechanism, and enhances MYC-dependent transcription and cancer cell survival. These results demonstrate that ecDNA fosters genome instability and frequent oncogene fusion formation in cancer.

논문정보

형식Research article
게재일2026년 01월 (BRIC 등록일 2026-01-08)
연구진국외 연구진
분야 생명과학 > 분자생물학

이혜림 님 전체 논문보기

연구자 ID

댓글 작성 로그인

CV 열람하기

연락처 보기