Contact

  • Academic
    skpritch@stanford.edu
    University - Student Department: Biology Position: Undergraduate
    University - Student Department: Statistics Position: Graduate

Additional Info

All Publications

  • EcDNA-borne structural variants drive oncogenic fusion transcript amplification. Cell Yi, H., Zhang, S., Swinderman, J., Wang, Y., Kanakaveti, V., Hung, K. L., Tsz-Lo Wong, I., Srinivasan, S., Curtis, E. J., Bhargava-Shah, A., Li, R., Jones, M. G., Luebeck, J., Bailey, C., Zhao, Y., Belk, J. A., Kraft, K., Shi, Q., Yan, X., Pritchard, S. K., Mahajan, K. S., Liang, F., Jamal-Hanjani, M., Felsher, D. W., Gilbert, L. A., Bafna, V., Mischel, P. S., Chang, H. Y. 2026

    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.

    View details for DOI 10.1016/j.cell.2025.12.009

    View details for PubMedID 41506267

https://orcid.org/0009-0008-4013-515X