染色体非整倍体作为人类癌症的驱动因素
Aneuploidy as a driver of human cancer
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影响因子:29
分区:生物学1区 Top / 遗传学1区
发表日期:2024 Oct
作者:
Eran Sdeor, Hajime Okada, Ron Saad, Tal Ben-Yishay, Uri Ben-David
DOI:
10.1038/s41588-024-01916-2
摘要
非整倍体，即染色体异常数目，是癌症发生和发展的主要驱动因素，也是癌症治疗反应和临床预后的重要决定因素。尽管被认为是人类癌症的标志之一，但非整倍体作为“驱动”因素的具体作用尚不完全清楚。识别导致常见非整倍体反复出现的具体遗传元素，是癌症遗传学面临的重大挑战。本综述讨论了反复出现的非整倍体及其作为肿瘤发生驱动因素的作用，重点介绍了在不同背景下识别和功能鉴定驱动基因的方法，以及利用癌症基因组学数据和模型探索这些驱动基因的新策略。最后，探讨了利用这些常见基因变异的功能后果，针对驱动非整倍体的潜在治疗策略。
Abstract
Aneuploidy, an abnormal chromosome composition, is a major contributor to cancer development and progression and an important determinant of cancer therapeutic responses and clinical outcomes. Despite being recognized as a hallmark of human cancer, the exact role of aneuploidy as a 'driver' of cancer is still largely unknown. Identifying the specific genetic elements that underlie the recurrence of common aneuploidies remains a major challenge of cancer genetics. In this Review, we discuss recurrent aneuploidies and their function as drivers of tumor development. We then delve into the context-dependent identification and functional characterization of the driver genes underlying driver aneuploidies and examine emerging strategies to uncover these driver genes using cancer genomics data and cancer models. Lastly, we explore opportunities for targeting driver aneuploidies in cancer by leveraging the functional consequences of these common genetic alterations.