Extrachromosomal circular SUZ12 amplicon dictates retinoblastoma progression through reprogramming H3K27 methylation [eccDNA-seq]

Extrachromosomal circular DNA (eccDNA) is double-stranded circular DNA that is derived from but independent of chromosomal DNA. Owing to its nonchromosomal inheritance, eccDNA facilitates the amplification of oncogenes and expedites the process of genome evolution in tumor. However, the role of eccDNA in RB remains enigmatic. We combined Circle-Seq and RNA-Seq to identified crucial extrachromosomal circular oncogene amplicons. Herein, we revealed that extrachromosomal circular SUZ12 amplicon regulates H3K27me3 modification during the oncogenic progression of retinoblastoma. Conclusively, our study initially delineated an integrated picture of the eccDNA landscape in retinoblastoma and unveiled a novel SUZ12-containing eccDNA/H3K27me3 oncogenic mechanism where eccDNA dictates retinoblastoma progression through regulating transcription levels of linear DNA. To identified crucial extrachromosomal circular oncogene amplicons in retinoblastoma

染色体外环状DNA（extrachromosomal circular DNA, eccDNA）是一类源于染色体DNA但独立于其存在的双链环状DNA分子。由于其染色体外遗传特性，eccDNA可促进癌基因扩增，并加速肿瘤的基因组进化进程。然而，eccDNA在视网膜母细胞瘤（retinoblastoma, RB）中的作用仍未明确。本研究结合Circle-Seq与RNA-Seq技术，鉴定出关键的染色体外环状癌基因扩增子。本研究揭示，染色体外环状SUZ12扩增子在视网膜母细胞瘤的致癌进程中可调控H3K27me3修饰。综上，本研究首次描绘了视网膜母细胞瘤中eccDNA的整体图谱，并揭示了一种包含SUZ12的新型eccDNA/H3K27me3致癌机制：eccDNA通过调控线性DNA的转录水平，决定视网膜母细胞瘤的进展。本研究旨在鉴定视网膜母细胞瘤中的关键染色体外环状癌基因扩增子。