癌症染色体外DNA。

IF 7.7 2区 生物学 Q1 GENETICS & HEREDITY
Vineet Bafna, Paul S Mischel
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引用次数: 10

摘要

在癌症中,复杂的基因组重排和其他结构改变,包括环状染色体外DNA(ecDNA)元件上致癌基因的扩增,驱动肿瘤的形成和发展。ecDNA是一种特别具有挑战性的结构改变。通过将癌基因从染色体限制中分离出来,它提高了癌基因拷贝数,驱动了肿瘤内的遗传异质性,促进了肿瘤的快速进化,并导致了治疗耐药性。ecDNA产生的DNA形状和核结构的深刻变化通过催化染色体上没有发生的新型调控相互作用,改变了肿瘤的转录格局。目前用于询问癌症基因组的一套工具非常适合于破译序列,但解决ecDNA产生的DNA结构和动力学的复杂变化的能力有限。在这里,我们回顾了解决ecDNA形式和功能的挑战,并讨论了新出现的破译ecDNA结构和空间组织的工具包,包括迄今为止对这种形状的巨大变化如何改变肿瘤的发展、进展和耐药性的了解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Extrachromosomal DNA in Cancer.

In cancer, complex genome rearrangements and other structural alterations, including the amplification of oncogenes on circular extrachromosomal DNA (ecDNA) elements, drive the formation and progression of tumors. ecDNA is a particularly challenging structural alteration. By untethering oncogenes from chromosomal constraints, it elevates oncogene copy number, drives intratumoral genetic heterogeneity, promotes rapid tumor evolution, and results in treatment resistance. The profound changes in DNA shape and nuclear architecture generated by ecDNA alter the transcriptional landscape of tumors by catalyzing new types of regulatory interactions that do not occur on chromosomes. The current suite of tools for interrogating cancer genomes is well suited for deciphering sequence but has limited ability to resolve the complex changes in DNA structure and dynamics that ecDNA generates. Here, we review the challenges of resolving ecDNA form and function and discuss the emerging tool kit for deciphering ecDNA architecture and spatial organization, including what has been learned to date about how this dramatic change in shape alters tumor development, progression, and drug resistance.

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来源期刊
CiteScore
14.90
自引率
1.10%
发文量
29
期刊介绍: Since its inception in 2000, the Annual Review of Genomics and Human Genetics has been dedicated to showcasing significant developments in genomics as they pertain to human genetics and the human genome. The journal emphasizes genomic technology, genome structure and function, genetic modification, human variation and population genetics, human evolution, and various aspects of human genetic diseases, including individualized medicine.
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