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利用病毒DNA靶向、消灭癌细胞

 医学abeycd 2019-12-07

论文标题:LTR retroelement expansion of the human cancer transcriptome and immunopeptidome revealed by de novo transcript assembly

作者:Jan Attig1, George R. Young2, Louise Hosie1, David Perkins3, Vesela Encheva-Yokoya3, Jonathan P. Stoye2, Ambrosius P. Snijders3, Nicola Ternette5 and George Kassiotis1

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期刊:Genome Research

发表时间:2019/09/19

数字识别码:10.1101/gr.248922.119

摘要:Dysregulated endogenous retroelements (EREs) are increasingly implicated in the initiation, progression, and immune surveillance of human cancer. However, incomplete knowledge of ERE activity limits mechanistic studies. By using pan-cancer de novo transcript assembly, we uncover the extent and complexity of ERE transcription. The current assembly doubled the number of previously annotated transcripts overlapping with long-terminal repeat (LTR) elements, several thousand of which were expressed specifically in one or a few related cancer types. Exemplified in melanoma, LTR-overlapping transcripts were highly predictable, disease prognostic, and closely linked with molecularly defined subtypes. They further showed the potential to affect disease-relevant genes, as well as produce novel cancer-specific antigenic peptides. This extended view of LTR elements provides the framework for functional validation of affected genes and targets for cancer immunotherapy.

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所属学科:

生物

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基因转录成mRNA的过程,可能会受到来自逆转录病毒等外源DNA的影响。经历与病毒的漫长斗争后,人类基因组上已经有8%的基因来自逆转录病毒。这些病毒DNA通常处于休眠状态,然而,当细胞癌变时,它们可以被重新激活。近日发表在《基因组研究》上的数据表明,以黑色素瘤为例,基因组上有8个不同区域会产生独特的肿瘤抗原,即这些基因区域是癌变后重新被激活的。研究团队希望在未来利用该特性帮助免疫系统,识别并攻击含有这些抗原的癌细胞。  

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