人们经常在癌细胞中发现细胞核外染色体。不过根据2012年1月18日发表在《自然》期刊上的一项研究，美国达纳法伯癌症研究所(Dana-Farber Cancer Institute)研究人员发现细胞核外染色体可能在癌症形成上也发挥着一种作用。在细胞质中染色体被它们自己的膜包围，在细胞分裂期间有着较高的断裂率和重排率，从而潜在性地促进癌症转换。
这些所谓的微核(micronuclei)一直令研究人员感到迷惑，因为他们不确定这些微小的细胞器是遗传不稳定的癌细胞产生的，还是促进癌症形成的因子。因此这项研究的研究人员对这些微核进行染色，然后追踪它们的细胞复制周期。尽管细胞核染色体能够正常复制，但是微核要在细胞完成分裂之后较长时间才继续复制过程。因为染色体不是在合适的环境中复制，所以它们经常在微核中断裂为较短的片段。这些片段并不丢弃，在下一次复制周期期间会传递给子细胞，并整合进细胞核染色体中，潜在性地促进完整基因组发生促进癌症产生的错误。
该研究论文通讯作者David Pellman说，尽管染色体片段的错误整合只发生“少数的人癌症中，但是我们的研究发现提示着它或许是一类可能更加常见的染色体损伤的一种极端例子”。(生物谷：towersimper编译)
doi:10.1038/nature10802
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DNA breaks and chromosome pulverization from errors in mitosis
Karen Crasta, Neil J. Ganem, Regina Dagher, Alexandra B. Lantermann, Elena V. Ivanova, Yunfeng Pan, Luigi Nezi, Alexei Protopopov, Dipanjan Chowdhury & David Pellman
The involvement of whole-chromosome aneuploidy in tumorigenesis is the subject of debate, in large part because of the lack of insight into underlying mechanisms. Here we identify a mechanism by which errors in mitotic chromosome segregation generate DNA breaks via the formation of structures called micronuclei. Whole-chromosome-containing micronuclei form when mitotic errors produce lagging chromosomes. We tracked the fate of newly generated micronuclei and found that they undergo defective and asynchronous DNA replication, resulting in DNA damage and often extensive fragmentation of the chromosome in the micronucleus. Micronuclei can persist in cells over several generations but the chromosome in the micronucleus can also be distributed to daughter nuclei. Thus, chromosome segregation errors potentially lead to mutations and chromosome rearrangements that can integrate into the genome. Pulverization of chromosomes in micronuclei may also be one explanation for ‘chromothripsis’ in cancer and developmental disorders, where isolated chromosomes or chromosome arms undergo massive local DNA breakage and rearrangement.
