This research explores how extrachromosomal DNA (ecDNA) functions as a primary catalyst for gene fusions and oncogene amplification in various human cancers. The study identifies that ecDNA-borne fusions, particularly those involving the PVT1 lncRNA, significantly enhance the stability of oncogenic transcripts like MYC. Mechanistically, the PVT1 exon 1 segment binds to the protein SRSF1, allowing the resulting fusion RNA to evade standard cellular degradation pathways. This interaction increases the half-life of cancer-driving messages, leading to higher protein levels and increased tumor fitness. Ultimately, these findings reveal that ecDNA promotes malignancy not just through increased gene copies, but by creating stabilized fusion transcripts that resist suppression.

References:

• Yi H, Zhang S, Swinderman J, et al. EcDNA-borne structural variants drive oncogenic fusion transcript amplification[J]. Cell, 2026.