Stevens Joshua B, Liu Guo, Bremer Steven W, Ye Karen J, Xu Wenxin, Xu Jing, Sun Yi, Wu Gen Sheng, Savasan Sureyya, Krawetz Stephen A, Ye Christine J, Heng Henry H Q
Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
Cancer Res. 2007 Aug 15;67(16):7686-94. doi: 10.1158/0008-5472.CAN-07-0472.
Cell death plays a key role for both cancer progression and treatment. In this report, we characterize chromosome fragmentation, a new type of cell death that takes place during metaphase where condensed chromosomes are progressively degraded. It occurs spontaneously without any treatment in instances such as inherited status of genomic instability, or it can be induced by treatment with chemotherapeutics. It is observed within cell lines, tumors, and lymphocytes of cancer patients. The process of chromosome fragmentation results in loss of viability, but is apparently nonapoptotic and further differs from cellular death defined by mitotic catastrophe. Chromosome fragmentation represents an efficient means of induced cell death and is a clinically relevant biomarker of mitotic cell death. Chromosome fragmentation serves as a method to eliminate genomically unstable cells. Paradoxically, this process could result in genome aberrations common in cancer. The characterization of chromosome fragmentation may also shine light on the mechanism of chromosomal pulverization.
细胞死亡在癌症进展和治疗中都起着关键作用。在本报告中，我们描述了染色体片段化，这是一种在中期发生的新型细胞死亡，在此过程中浓缩的染色体逐渐降解。它在诸如基因组不稳定的遗传状态等情况下无需任何处理即可自发发生，或者可以通过化疗药物处理来诱导。在癌症患者的细胞系、肿瘤和淋巴细胞中均可观察到。染色体片段化过程会导致细胞活力丧失，但显然是非凋亡性的，并且进一步不同于由有丝分裂灾难定义的细胞死亡。染色体片段化代表了一种诱导细胞死亡的有效方式，并且是有丝分裂细胞死亡的临床相关生物标志物。染色体片段化可作为一种消除基因组不稳定细胞的方法。矛盾的是，这个过程可能会导致癌症中常见的基因组畸变。染色体片段化的特征描述也可能有助于揭示染色体粉碎的机制。
