Spatial-Temporal Diversity of Extrachromosomal DNA Shapes Urothelial Carcinoma Evolution and the Tumor Immune Microenvironment

Wei Lv^#^{1

2

3}, Yuchen Zeng^#¹, Conghui Li^#⁴, Yuan Liang^#⁵, Huiying Tao⁶, Yanfen Zhu⁷, Xiaolong Sui⁶, Yue Li⁶, Shiqi Jiang¹, Qingqing Gao¹, Elias Rodriguez-Fos^{8

9}, Gino Prasad¹⁰, Yuanmei Wang¹, Run Zhou¹, Zhe Xu¹¹, Xiaoguang Pan^{4

11}, Linlin Chen¹, Xi Xiang¹², Huajing Teng¹³, Chaoyang Sun^{14

15}, Tianyu Qin^{14

15}, Wei Dong¹, Yongwei Li⁶, Xun Lan¹⁶, Xuesong Li¹⁷, Lin Lin³, Lars Bolund^{1

3

11}, Huanming Yang¹, Roel G W Verhaak¹⁸, Bishoy M Faltas^{19

20

21

22}, Jacob B Hansen⁴, Sihan Wu²³, Paul S Mischel^{24

25}, Anton G Henssen^{8

9

26

27}, Vineet Bafna^{10

28}, Jens Luebeck¹⁰, Birgitte Regenberg⁴, Yonglun Luo³, Chunhua Lin⁶, Peng Han^{11

12}

Affiliations

¹ HIM-BGI Omics Center, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China.
² Department of Urology & Andrology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
³ Department of Biomedicine, Aarhus University, Aarhus, Denmark.
⁴ Department of Biology, University of Copenhagen, Copenhagen, Denmark.
⁵ CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing, China.
⁶ Department of Urology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China.
⁷ The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, China.
⁸ Department of Pediatric Oncology and Hematology, Charité - Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
⁹ Experimental and Clinical Research Center of the MDC and Charité Berlin, Berlin, Germany.
¹⁰ Department of Computer Science and Engineering, University of California at San Diego, San Diego, California.
¹¹ Lars Bolund Institute of Regenerative Medicine, Qingdao-Europe Advanced Institute for Life Sciences, Qingdao, China.
¹² Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China.
¹³ Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing, China.
¹⁴ Department of Gynecological Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
¹⁵ National Clinical Research Center for Obstetrics and Gynecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
¹⁶ Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China.
¹⁷ Department of Urology, Peking University First Hospital, Beijing, China.
¹⁸ Department of Neurosurgery, Yale School of Medicine, New Haven, Connecticut.
¹⁹ Department of Medicine, Weill Cornell Medicine, New York, New York.
²⁰ Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, New York.
²¹ Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, New York.
²² Department of Cell and Developmental Biology, Weill Cornell Medicine, New York, New York.
²³ Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, Texas.
²⁴ Department of Pathology, Stanford University School of Medicine, Stanford, California.
²⁵ Sarafan Chemistry, Engineering, and Medicine for Human Health (Sarafan ChEM-H), Stanford University, Stanford, California.
²⁶ Max-Delbrück-Centrum für Molekulare Medizin, Berlin, Germany.
²⁷ German Cancer Consortium, partner site Berlin, and German Cancer Research Center, Heidelberg, Germany.
²⁸ Halıcıoğlu Data Science Institute, University of California at San Diego, San Diego, California.

^# Contributed equally.

PMID: 40331621
DOI: 10.1158/2159-8290.CD-24-1532

Spatial-Temporal Diversity of Extrachromosomal DNA Shapes Urothelial Carcinoma Evolution and the Tumor Immune Microenvironment

Wei Lv et al. Cancer Discov. 2025.

. 2025 May 7:OF1-OF22.

doi: 10.1158/2159-8290.CD-24-1532. Online ahead of print.

Authors

Affiliations

¹ HIM-BGI Omics Center, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China.
² Department of Urology & Andrology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
³ Department of Biomedicine, Aarhus University, Aarhus, Denmark.
⁴ Department of Biology, University of Copenhagen, Copenhagen, Denmark.
⁵ CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing, China.
⁶ Department of Urology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China.
⁷ The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, China.
⁸ Department of Pediatric Oncology and Hematology, Charité - Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
⁹ Experimental and Clinical Research Center of the MDC and Charité Berlin, Berlin, Germany.
¹⁰ Department of Computer Science and Engineering, University of California at San Diego, San Diego, California.
¹¹ Lars Bolund Institute of Regenerative Medicine, Qingdao-Europe Advanced Institute for Life Sciences, Qingdao, China.
¹² Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China.
¹³ Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing, China.
¹⁴ Department of Gynecological Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
¹⁵ National Clinical Research Center for Obstetrics and Gynecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
¹⁶ Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China.
¹⁷ Department of Urology, Peking University First Hospital, Beijing, China.
¹⁸ Department of Neurosurgery, Yale School of Medicine, New Haven, Connecticut.
¹⁹ Department of Medicine, Weill Cornell Medicine, New York, New York.
²⁰ Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, New York.
²¹ Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, New York.
²² Department of Cell and Developmental Biology, Weill Cornell Medicine, New York, New York.
²³ Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, Texas.
²⁴ Department of Pathology, Stanford University School of Medicine, Stanford, California.
²⁵ Sarafan Chemistry, Engineering, and Medicine for Human Health (Sarafan ChEM-H), Stanford University, Stanford, California.
²⁶ Max-Delbrück-Centrum für Molekulare Medizin, Berlin, Germany.
²⁷ German Cancer Consortium, partner site Berlin, and German Cancer Research Center, Heidelberg, Germany.
²⁸ Halıcıoğlu Data Science Institute, University of California at San Diego, San Diego, California.

^# Contributed equally.

PMID: 40331621
DOI: 10.1158/2159-8290.CD-24-1532

Abstract

Our comprehensive analysis of ecDNA in urothelial carcinoma reveals its crucial role in driving the evolution and heterogeneity of multifocal cancer, as well as its early involvement in tumorigenesis. Moreover, this study sheds light on immune evasion mechanisms associated with ecDNA and offers valuable insights for developing targeted therapeutic strategies.

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Spatial-Temporal Diversity of Extrachromosomal DNA Shapes Urothelial Carcinoma Evolution and the Tumor Immune Microenvironment

Affiliations

Spatial-Temporal Diversity of Extrachromosomal DNA Shapes Urothelial Carcinoma Evolution and the Tumor Immune Microenvironment

Authors

Affiliations

Abstract

Grants and funding

LinkOut - more resources

Full Text Sources