染色体粉碎——基因组灾难性事件产物

"染色体粉碎"是最初在肿瘤细胞中发现的一种复杂的基因组重排现象.在该事件中,细胞的一条或几条染色体在短时间内发生大量的DNA双链断裂,形成小的DNA碎片,之后这些碎片被细胞的DNA修复机制随机地拼接起来,形成新的染色体.染色体粉碎事件会造成大量的基因组重排,引起DNA拷贝数的变异和基因融合,从而导致正常细胞向肿瘤细胞的快速转化.这与传统的癌症发生理论不同,传统理论认为肿瘤的发生是由基因突变逐步积累而导致的,因此染色体粉碎现象可能揭示了一种肿瘤发生的新机制.目前,该现象的内在机制还不完全清楚,其判别标准也存在争议.本文综述了近年来关于染色体粉碎现象的判别标准和产生机制,探讨了该现象与肿瘤发生发展的关系,为进一步研究染色体粉碎事件提供参考.

Chromothripsis, The Consequence of Genomic Catastrophe

Chromothripsis is a type of complex chromosomal rearrangements that was originally observed in cancer cells. In this event, one or several chromosomes of the cell shatter into pieces, and then randomly reassembled to create derivative chromosomes. This type of event generates a great number of chromosomal rearrangements, DNA copy number aberrations and fusion genes. It will convert a normal cell to a cancer cell in relatively short-time period. This is different from the classical theory of cancer initiation, in which gene mutations are accumulated step-by-step. Thus, chromothripsis may reveal a new paradigm in cancer initiation. The molecular mechanisms of this phenomenon are not fully understood, and some controversy exists in terms of chromothripsis detection criteria. This review highlights recent advances made in the chromothripsis identification criteria and mechanisms. We also discussed the relationship between chromothripsis and cancer initiation and progression. It provides a reference for further chromothripsis research.