Research progress on chromothripsis and tumorigenesis

Huanliang MENG; Haoran MU; Yafei JIANG; Kai TIAN; Enjun HE; Yingqi HUA

doi:10.19401/j.cnki.1007-3639.2023.04.009

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Research progress on chromothripsis and tumorigenesis

Review | 更新时间：2025-12-31

- Research progress on chromothripsis and tumorigenesis
- China Oncology Vol. 33, Issue 4, Pages: 388-396(2023)
- 作者机构：
  
  上海交通大学医学院附属第一人民医院骨肿瘤科，上海 200080
- 作者简介：
  
  HUA Yingqi.
- 基金信息：
- DOI：10.19401/j.cnki.1007-3639.2023.04.009
  CLC： R730.2
- Received：18 May 2022，
  
  Revised：2022-10-23，
  
  Published：30 April 2023
- 稿件说明：
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Huanliang MENG, Haoran MU, Yafei JIANG, et al. Research progress on chromothripsis and tumorigenesis[J]. China Oncology, 2023, 33(4): 388-396.
DOI：

Huanliang MENG, Haoran MU, Yafei JIANG, et al. Research progress on chromothripsis and tumorigenesis[J]. China Oncology, 2023, 33(4): 388-396. DOI： 10.19401/j.cnki.1007-3639.2023.04.009.

摘要

染色体碎裂是在应激（电离辐射、化学刺激、感染等）刺激下一条或几条染色体局部区域发生碎裂，然后以随机顺序组合在一起的复杂性基因组重排事件。近年来，通过全基因组测序、单核苷酸多态性阵列、比较基因组杂交等技术发现，这种高度复杂的基因组畸变事件普遍存在于各类型的肿瘤中，在肉瘤和神经系统肿瘤中的发生频率较高。发生染色体碎裂的机制尚不清楚，目前已知有两种主要的染色体碎裂形成机制：① 微核的形成及微核内染色体的碎裂；② 断裂-融合-桥循环的产生。染色体碎裂对于绝大多数细胞来说是灾难性的，但仍有部分细胞在经历此过程后存活下来，细胞内碎裂的染色体片段通过非同源末端连接、交替端部连接及微同源介导的断裂诱导复制等修复方式随机组合使基因组发生重排，重排后的基因组可能出现癌基因的扩增、抑癌基因的删除或者形成融合基因，赋予细胞显著的选择性生长优势，推动肿瘤的发生、发展。近年来的临床队列研究显示，肿瘤患者的临床预后也与染色体碎裂发生频率有关。染色体碎裂发生的频率越高，患者的预后越差。肿瘤中发生染色体碎裂的普遍性以及较差的预后提示检测染色体碎裂可能是评估肿瘤患者生存及预后的一种方式。已有研究表明，染色体碎裂在肿瘤的发生、发展过程中起着重要作用，但目前有关染色体碎裂现象的原因、导致肿瘤发生的机制、染色体碎裂的诊断及治疗等问题仍有待深入研究。随着对染色体碎裂相关问题的解答，将有助于更好地理解染色体碎裂在肿瘤进展中的作用，为肿瘤的预防及治疗提供新的理论依据。本文就染色体碎裂与肿瘤发生研究进展进行综述。

Abstract

Chromothripsis is a complex genomic rearrangement event in which localized regions of one or several chromosomes fragment in response to stress (ionizing radiation

chemical stimulation

infection

etc.) and then assembles in random order. In recent years

through whole genome sequencing

single nucleotide polymorphism array

comparative genome hybridization and other technologies

it has been found that such highly complex genomic aberration events are common in all types of tumors

and they occur more frequently in sarcoma and nervous system tumors. The mechanism of chromothripsis is not clear

and there are two main mechanisms of chromothripsis formation: ① Formation of micronuclei and fragmentation of chromosomes in micronuclei; ② Generation of breakage-fusion-bridge cycles. Chromothripsis is catastrophic for the vast majority of cells

but some cells still survive this process. The fragmented chromosome fragments in cells are randomly combined to cause genome rearrangement through non-homologous end-joining

alternative end joining and microhomology-mediated break-induced replication. Oncogene amplification

tumor suppressor gene deletion or fusion gene formation may occur in the rearranged genome

which endowing cells with significant selective growth advantages and promoting the occurrence and development of tumors. Some criteria have been proposed to infer whether chromothripsis occurs in the genome. Recent clinical cohort studies have shown that the clinical prognosis of cancer patients is also related to the frequency of chromothripsis. The higher the frequency of chromothripsis

the worse the prognosis. The prevalence and poor prognosis of chromothripsis in tumors suggest that detection of chromothripsis may be a way to evaluate the survival and prognosis of cancer patients. It has been found that chromothripsis plays an important role in the occurrence and development of tumors

however

the causes of chromothripsis

the mechanism of tumorigenesis

the diagnosis and treatment of chromothripsis remain to be further studied. With the answers to the related questions of chromothripsis

it will be helpful to better understand the role of chromothripsis in tumor progression

and provide a new theoretical basis for the prevention and treatment of cancer. This article reviewed the research progress of chromothripsis and tumorigenesis.

关键词

Keywords

references

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