Transcriptional immune suppression and upregulation of double stranded DNA damage and repair repertoires in ecDNA-containing tumors.
Transcriptional immune suppression and upregulation of double stranded DNA damage and repair repertoires in ecDNA-containing tumors.
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含有 ecDNA 的肿瘤中双链 DNA 损伤和修复库的转录免疫抑制和上调。
DOI：
10.1101/2023.04.24.537925
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Bafna,Vineet
中科院分区：
文献类型：
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作者：
Lin,MiinS;Jo,Se-Young;Luebeck,Jens;Chang,HowardY;Wu,Sihan;Mischel,PaulS;Bafna,Vineet
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，导致患者的治疗抗性和不良结局。ecDNAs产生和发展的转录背景，包括染色体驱动的转录，还没有完全理解。我们研究了870个不同组织学类型的肿瘤的基因表达模式，以确定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。具体而言，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，这些结果表明在含有ecDNA的肿瘤中基因调控发生了深刻的变化，揭示了导致其发展和进展的分子过程。
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.