Chan Sock Hoai, Ngeow Joanne
Division of Medical OncologyCancer Genetics Service, National Cancer Centre Singapore, Singapore.
Division of Medical OncologyCancer Genetics Service, National Cancer Centre Singapore, Singapore
Endocr Relat Cancer. 2017 Sep;24(9):T33-T46. doi: 10.1530/ERC-17-0062.
Genomic instability is a feature of cancer that fuels oncogenesis through increased frequency of genetic disruption, leading to loss of genomic integrity and promoting clonal evolution as well as tumor transformation. A form of genomic instability prevalent across cancer types is chromosomal instability, which involves karyotypic changes including chromosome copy number alterations as well as gross structural abnormalities such as transversions and translocations. Defects in cellular mechanisms that are in place to govern fidelity of chromosomal segregation, DNA repair and ultimately genomic integrity are known to contribute to chromosomal instability. In this review, we discuss the association of germline mutations in these pathways with chromosomal instability in the background of related cancer predisposition syndromes. We will also reflect on the impact of genetic predisposition to clinical management of patients and how we can exploit this vulnerability to promote catastrophic genomic instability as a therapeutic strategy.
基因组不稳定是癌症的一个特征，它通过增加基因破坏的频率来推动肿瘤发生，导致基因组完整性丧失，并促进克隆进化以及肿瘤转化。一种在各种癌症类型中普遍存在的基因组不稳定形式是染色体不稳定，它涉及核型变化，包括染色体拷贝数改变以及诸如颠换和易位等严重的结构异常。已知负责控制染色体分离、DNA修复以及最终基因组完整性保真度的细胞机制缺陷会导致染色体不稳定。在这篇综述中，我们讨论了这些途径中的种系突变与相关癌症易感综合征背景下的染色体不稳定之间的关联。我们还将思考遗传易感性对患者临床管理的影响，以及我们如何利用这种易损性来促进灾难性的基因组不稳定作为一种治疗策略。
