Telethon Kids Cancer Centre, Telethon Kids Institute, Perth, WA 6009, Australia.
Curtin Medical School, Curtin University, Perth, WA 6102, Australia.
Int J Mol Sci. 2024 Jun 21;25(13):6815. doi: 10.3390/ijms25136815.
Copy number alterations (CNAs), resulting from the gain or loss of genetic material from as little as 50 base pairs or as big as entire chromosome(s), have been associated with many congenital diseases, de novo syndromes and cancer. It is established that CNAs disturb the dosage of genomic regions including enhancers/promoters, long non-coding RNA and gene(s) among others, ultimately leading to an altered balance of key cellular functions. In cancer, CNAs have been associated with almost all steps of the disease: predisposition, initiation, development, maintenance, response to treatment, resistance, and relapse. Therefore, understanding how specific CNAs contribute to tumourigenesis may provide prognostic insight and ultimately lead to the development of new therapeutic approaches to improve patient outcomes. In this review, we provide a snapshot of what is currently known about CNAs and cancer, incorporating topics regarding their detection, clinical impact, origin, and nature, and discuss the integration of innovative genetic engineering strategies, to highlight the potential for targeting CNAs using novel, dosage-sensitive and less toxic therapies for CNA-driven cancer.
拷贝数改变（CNAs），源自于从少至 50 个碱基对至整个染色体（s）的遗传物质的增益或损失，与许多先天性疾病、新生综合征和癌症有关。已证实 CNAs 扰乱了基因组区域的剂量，包括增强子/启动子、长非编码 RNA 和基因（s）等，最终导致关键细胞功能的失衡。在癌症中，CNAs 与疾病的几乎所有步骤都有关：易感性、起始、发展、维持、对治疗的反应、耐药性和复发。因此，了解特定的 CNAs 如何促进肿瘤发生可能提供预后见解，并最终导致开发新的治疗方法来改善患者的预后。在这篇综述中，我们提供了目前关于 CNAs 和癌症的一些信息，包括关于它们的检测、临床影响、起源和性质的主题，并讨论了创新的基因工程策略的整合，以突出使用新型、剂量敏感和毒性较小的疗法针对 CNA 驱动的癌症的潜力。
