Cold Spring Harbor Laboratory School of Biological Sciences, Cold Spring, Harbor, NY 11724, USA.
Yale University School of Medicine, New Haven, CT 06511, USA.
Trends Genet. 2023 Dec;39(12):968-980. doi: 10.1016/j.tig.2023.09.002. Epub 2023 Sep 29.
Chromosome copy number imbalances, otherwise known as aneuploidies, are a common but poorly understood feature of cancer. Here, we describe recent advances in both detecting and manipulating aneuploidies that have greatly advanced our ability to study their role in tumorigenesis. In particular, new clustered regularly interspaced short palindromic repeats (CRISPR)-based techniques have been developed that allow the creation of isogenic cell lines with specific chromosomal changes, thereby facilitating experiments in genetically controlled backgrounds to uncover the consequences of aneuploidy. These approaches provide increasing evidence that aneuploidy is a key driver of cancer development and enable the identification of multiple dosage-sensitive genes encoded on aneuploid chromosomes. Consequently, measuring aneuploidy may inform clinical prognosis, while treatment strategies that target aneuploidy could represent a novel method to counter malignant growth.
染色体拷贝数不平衡，也称为非整倍体，是癌症的一个常见但尚未被充分理解的特征。在这里，我们描述了在检测和操纵非整倍体方面的最新进展，这些进展极大地提高了我们研究其在肿瘤发生中的作用的能力。特别是，新的基于簇状规律间隔的短回文重复序列（CRISPR）的技术已经被开发出来，这些技术允许创建具有特定染色体变化的同基因细胞系，从而在遗传控制背景下进行实验，以揭示非整倍体的后果。这些方法提供了越来越多的证据表明，非整倍体是癌症发展的关键驱动因素，并能够识别在非整倍体染色体上编码的多个剂量敏感基因。因此，测量非整倍体可能有助于临床预后，而针对非整倍体的治疗策略可能代表一种对抗恶性生长的新方法。
