Bioinformatics and Systems Biology Graduate Program, University of California, San Diego, La Jolla, United States.
Department of Biomedical Systems Informatics and Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea.
Elife. 2024 Jun 19;12:RP88895. doi: 10.7554/eLife.88895.
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.
染色体外 DNA 是癌症中癌基因扩增的常见原因。ecDNA 的非染色体遗传使肿瘤能够快速进化，导致治疗耐药和患者预后不良。ecDNA 产生和进展的转录背景，包括染色体驱动的转录，尚未完全了解。我们检查了 870 种不同组织学类型的肿瘤的基因表达模式，以鉴定 ecDNA 的转录相关物。在这里，我们表明含有 ecDNA 的肿瘤影响四个主要的生物学过程。具体来说，含有 ecDNA 的肿瘤上调 DNA 损伤和修复、细胞周期控制和有丝分裂过程，但下调全局免疫调节途径。总之，这些结果表明 ecDNA 含有肿瘤中的基因调控发生了深刻的改变，揭示了导致其发展和进展的分子过程。
