Chromosomal instability (CIN) is one of the characteristics of cancer inherent for tumor initiation and progression, which is defined as a persistent, high rate of gain/loss of whole chromosomes. In the vast majority of human tumors the molecular basis of CIN remains unknown. The development of a conceptually simple colony color sectoring assay that measures yeast artificial chromosome (YAC) loss provided a powerful genetic tool to assess the rate of chromosome mis-segregation and also identified 937 yeast genes involved in this process. Similarly, a human artificial chromosome (HAC)-based assay has been recently developed and applied to quantify chromosome mis-segregation events in human cells. This assay allowed identification of novel human CIN genes in the library of protein kinases. Among them are PINK1, TRIO, IRAK1, PNCK, and TAOK1. The HAC-based assay may be applied to screen siRNA, shRNA and CRISPR-based libraries to identify the complete spectrum of CIN genes. This will reveal new insights into mechanisms of chromosome segregation and may expedite the development of novel therapeutic strategies to target the CIN phenotype in cancer cells.

中文翻译：

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人类人工染色体（HAC），用于测量染色体不稳定性（CIN）和鉴定正确染色体传输所需的基因。

染色体不稳定性（CIN）是肿瘤发生和发展所固有的癌症特征之一，它被定义为整个染色体的持续，高速率的增/减。在绝大多数人类肿瘤中，CIN的分子基础仍然未知。测量酵母人工染色体（YAC）丢失的概念上简单的菌落颜色分区测定法的发展提供了一种强大的遗传工具，可评估染色体错误分离的速率，并且还鉴定了参与该过程的937个酵母基因。相似地，最近已经开发了基于人类人工染色体（HAC）的检测方法，并将其用于量化人类细胞中的染色体错误分离事件。该测定法允许鉴定蛋白激酶文库中的新型人CIN基因。其中包括PINK1，TRIO，IRAK1，PNCK和TAOK1。基于HAC的分析可用于筛选基于siRNA，shRNA和CRISPR的文库，以鉴定CIN基因的完整谱图。这将揭示对染色体分离机制的新见解，并可能加快针对癌细胞中CIN表型的新型治疗策略的发展。