Abstract：
Chromothripsis, a type of complex chromosomal rearrangement originally known as chromoanagenesis, has been a subject of extensive investigation due to its potential role in various diseases, particularly cancer. Chromothripsis involves the rapid acquisition of tens to hundreds of structural rearrangements within a short period, leading to complex alterations in one or a few chromosomes. This phenomenon is triggered by chromosome missegregation during mitosis. Errors in accurate chromosome segregation lead to formation of aberrant structural entities such as micronuclei or chromatin bridges. The association between chromothripsis and cancer has attracted significant interest, with potential implications for tumorigenesis and disease prognosis. This review aims to explore the intricate mechanisms and consequences of chromothripsis, with a specific focus on its association with mitotic perturbations. Herein, we discuss a comprehensive analysis of crucial molecular entities and pathways, exploring the intricate roles of the CIP2A-TOPBP1 complex, micronuclei formation, chromatin bridge processing, DNA damage repair, and mitotic checkpoints. Moreover, the review will highlight recent advancements in identifying potential therapeutic targets and the underlying molecular mechanisms associated with chromothripsis, paving the way for future therapeutic interventions in various diseases.
摘要：
嗜铬细胞增多症,一种复杂的染色体重排，最初被称为生色，由于其在各种疾病中的潜在作用，已成为广泛研究的主题，尤其是癌症。嗜铬细胞增多症涉及在短时间内快速获得数十到数百个结构重排，导致一个或几个染色体复杂的改变。这种现象是由有丝分裂过程中的染色体不分离引起的。精确染色体分离中的错误导致形成异常结构实体,例如微核或染色质桥。染色体与癌症之间的关联引起了极大的兴趣，对肿瘤发生和疾病预后有潜在影响。这篇综述旨在探讨染色体的复杂机制和后果，特别关注其与有丝分裂扰动的关联。在这里，我们讨论了对关键分子实体和途径的全面分析，探索CIP2A-TOPBP1复合物的复杂作用，微核形成，染色质桥处理，DNA损伤修复,和有丝分裂检查点。此外，这篇综述将重点介绍在确定潜在治疗靶点和与染色体相关的潜在分子机制方面的最新进展，为未来各种疾病的治疗干预铺平了道路。
