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染色体碎裂

Chromothripsis.

作者信息

Pellestor Franck, Ganne Benjamin, Gatinois Vincent

机构信息

Unit of Chromosomal Genetics and Research Platform Chromostem, Department of Molecular Genetics and Cytogenomics, Site Unique de Biologie (SUB), Montpellier CHU, Montpellier Cedex 5, France.

INSERM 1183 Unit "Genome and Stem Cell Plasticity in Development and Aging" Institute of Regenerative Medicine and Biotherapies, St Eloi Hospital, Montpellier, France.

出版信息

Methods Mol Biol. 2025;2968:3-33. doi: 10.1007/978-1-0716-4750-9_1.


DOI:10.1007/978-1-0716-4750-9_1
PMID:40884635
Abstract

The chromothripsis phenomenon is the first type of chaotic and complex rearrangements discovered since 2011 and now grouped together under the name of chromoanagenesis.Its occurrence has been documented in cancers, congenital diseases as well as in healthy individuals. The phenomenon has also been observed in many animal and plant species, suggesting that it is a mechanism of rapid and deep genome reorganization widely used in response to various cellular stresses.The determination of specific molecular characteristics has allowed chromothripsis to be better characterized and to be distinguished from other types of complex rearrangements. Various non-exclusive exogenous or cellular mechanisms capable of generating chromothripsis have been evoked. Recent experimental models have highlighted three major processes that can generate a cascade of cellular events leading to chromothripsis. These mechanisms are the formation of micronuclei integrating isolated chromosomal material, the occurrence of chromatin bridges around chromosomal material resulting from telomeric fusions, and the abortive apoptosis. In all cases, the cellular and molecular mechanisms of fragmentation, repair, and transmission of damaged chromosomal material are consistent with the characteristics of complex chromosomal rearrangements associated with chromothripsis.Undoubtedly, chromothripsis is one of the most unexpected biological discoveries to emerge from high-resolution genome analysis. As a mechanism for rapid genome modifications in germ lines and early development, chromothripsis supports the concept of macroevolution and can be regarded as a credible mechanism for speciation and organismal evolution.

摘要

染色体碎裂现象是自2011年以来发现的第一类混乱且复杂的重排类型,现在被归为染色体骤变这一类别。其发生已在癌症、先天性疾病以及健康个体中得到记录。该现象也在许多动植物物种中被观察到,这表明它是一种广泛用于应对各种细胞应激的快速且深度的基因组重组机制。特定分子特征的确定使得染色体碎裂能够得到更好的表征,并与其他类型的复杂重排区分开来。已经提出了各种能够产生染色体碎裂的非排他性外源或细胞机制。最近的实验模型突出了三个主要过程,这些过程可产生一系列导致染色体碎裂的细胞事件。这些机制包括整合孤立染色体物质的微核形成、端粒融合导致的围绕染色体物质的染色质桥的出现以及流产性凋亡。在所有情况下,受损染色体物质的断裂、修复和传递的细胞和分子机制都与染色体碎裂相关的复杂染色体重排特征一致。毫无疑问,染色体碎裂是高分辨率基因组分析中最意想不到的生物学发现之一。作为种系和早期发育中快速基因组修饰的一种机制,染色体碎裂支持宏观进化的概念,并且可被视为物种形成和生物进化的一种可信机制。

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本文引用的文献

[1]
Chromothripsis in cancer.

Nat Rev Cancer. 2025-2

[2]
Resolution of ring chromosomes, Robertsonian translocations, and complex structural variants from long-read sequencing and telomere-to-telomere assembly.

Am J Hum Genet. 2024-12-5

[3]
A national long-read sequencing study on chromosomal rearrangements uncovers hidden complexities.

Genome Res. 2024-11-20

[4]
Complex genomic rearrangements of the Y chromosome in a premature infant.

Mol Cytogenet. 2024-8-26

[5]
Chromothripsis is a novel biomarker for prognosis and differentiation diagnosis of pancreatic neuroendocrine neoplasms.

MedComm (2020). 2024-7-10

[6]
On the multiscale dynamics of punctuated evolution.

Trends Ecol Evol. 2024-8

[7]
Micronuclei induced by radiation, replication stress, or chromosome segregation errors do not activate cGAS-STING.

Mol Cell. 2024-6-6

[8]
Macromutations Yielding Karyotype Alterations (and the Process(es) behind Them) Are the Favored Route of Carcinogenesis and Speciation.

Cancers (Basel). 2024-1-28

[9]
Micronucleus is not a potent inducer of the cGAS/STING pathway.

Life Sci Alliance. 2024-4

[10]
Utility of long-read sequencing for All of Us.

Nat Commun. 2024-1-29

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