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染色体外环状DNA促进神经母细胞瘤致癌基因重塑
2019-12-18 13:50

美国纪念斯隆·凯特琳癌症中心Richard P. Koche课题组发现神经母细胞瘤中,染色体外环状DNA驱动致癌基因组重塑。这一研究成果2019年12月16日在线发表在国际学术期刊《自然—遗传学》上。

研究人员利用基因组学和转录组学相结合的方法描绘了神经母细胞瘤中染色体外环状DNA的图谱,神经母细胞瘤是儿童时期从交感神经系统原始细胞中产生的一种肿瘤。研究人员分析鉴定了一系列体细胞获得性和未知的染色体外环状DNA。此外,该研究发现染色体外环状DNA是偶发性体细胞重排的主要来源,通过嵌合环化和环状DNA重新整合到线性基因组中,导致致癌基因重塑。致癌性病变可从细胞周期引起的重排中产生,并与临床结果成负相关。细胞周期引起的重排很可能表征正在进行的诱变过程。因此,染色体外环状DNA代表多重突变诱变过程,对癌症基因组重塑具有重要的功能和临床意义。

研究人员表示,DNA的染色体外环化是癌症基因组的重要特征。然而,染色体外环状DNA的结构、组成以及全基因组发生频率尚未得到广泛的研究。

附:英文原文

Title: Extrachromosomal circular DNA drives oncogenic genome remodeling in neuroblastoma

Author: Richard P. Koche, Elias Rodriguez-Fos, Konstantin Helmsauer, Martin Burkert, Ian C. MacArthur, Jesper Maag, Rocio Chamorro, Natalia Munoz-Perez, Montserrat Puiggrs, Heathcliff Dorado Garcia, Yi Bei, Claudia Refzaad, Victor Bardinet, Annabell Szymansky, Annika Winkler, Theresa Thole, Natalie Timme, Katharina Kasack, Steffen Fuchs, Filippos Klironomos, Nina Thiessen, Eric Blanc, Karin Schmelz, Annette Knkele, Patrick Hundsdrfer, Carolina Rosswog, Jessica Theissen, Dieter Beule, Hedwig Deubzer, Sascha Sauer, Joern Toedling, Matthias Fischer, Falk Hertwig, Roland F. Schwarz, Angelika Eggert, David Torrents, Johannes H. Schulte, Anton G. Henssen

Issue&Volume: 2019-12-16

Abstract: Extrachromosomal circularization of DNA is an important genomic feature in cancer. However, the structure, composition and genome-wide frequency of extrachromosomal circular DNA have not yet been profiled extensively. Here, we combine genomic and transcriptomic approaches to describe the landscape of extrachromosomal circular DNA in neuroblastoma, a tumor arising in childhood from primitive cells of the sympathetic nervous system. Our analysis identifies and characterizes a wide catalog of somatically acquired and undescribed extrachromosomal circular DNAs. Moreover, we find that extrachromosomal circular DNAs are an unanticipated major source of somatic rearrangements, contributing to oncogenic remodeling through chimeric circularization and reintegration of circular DNA into the linear genome. Cancer-causing lesions can emerge out of circle-derived rearrangements and are associated with adverse clinical outcome. It is highly probable that circle-derived rearrangements represent an ongoing mutagenic process. Thus, extrachromosomal circular DNAs represent a multihit mutagenic process, with important functional and clinical implications for the origins of genomic remodeling in cancer.

DOI: 10.1038/s41588-019-0547-z

Source: https://www.nature.com/articles/s41588-019-0547-z

Nature Genetics:《自然—遗传学》,创刊于1992年。隶属于施普林格·自然出版集团,最新IF:41.307
官方网址:https://www.nature.com/ng/
投稿链接:https://mts-ng.nature.com/cgi-bin/main.plex


本期文章:《自然—遗传学》:Online/在线发表

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