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- Title
Transcriptional immune suppression and up-regulation of double-stranded DNA damage and repair repertoires in ecDNA-containing tumors.
- Authors
Lin, Miin S.; Se-Young Jo; Luebeck, Jens; Chang, Howard Y.; Sihan Wu; Mischel, Paul S.; Bafna, Vineet
- Abstract
Extrachromosomal DNA is a common cause of oncogene amplification in cancer. The non-chromosomal inheritance of ecDNA enables tumors to rapidly evolve, contributing to treatment resistance and poor outcome for patients. The transcriptional context in which ecDNAs arise and progress, including chromosomally-driven transcription, is incompletely understood. We examined gene expression patterns of 870 tumors of varied histological types, to identify transcriptional correlates of ecDNA. Here, we show that ecDNA-containing tumors impact four major biological processes. Specifically, ecDNA-containing tumors up-regulate DNA damage and repair, cell cycle control, and mitotic processes, but down-regulate global immune regulation pathways. Taken together, these results suggest profound alterations in gene regulation in ecDNA-containing tumors, shedding light on molecular processes that give rise to their development and progression.
- Subjects
DNA repair; DNA damage; IMMUNOSUPPRESSION; EXTRACHROMOSOMAL DNA; GENETIC regulation; DOUBLE-strand DNA breaks
- Publication
eLife, 2024, p1
- ISSN
2050-084X
- Publication type
Article
- DOI
10.7554/eLife.88895