非整倍性作为人类癌症的驱动力
Aneuploidy as a driver of human cancer
影响因子:29.00000
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
摘要
非整倍性是一种异常的染色体组成，是癌症发展和进展的主要因素，并且是癌症治疗反应和临床结果的重要决定因素。尽管被公认为是人类癌症的标志，但非整倍性作为癌症的“驱动力”的确切作用仍然在很大程度上是未知的。确定基于常见非整倍性复发的特定遗传因素仍然是癌症遗传学的主要挑战。在这篇综述中，我们讨论了复发性非整倍性及其作为肿瘤发育驱动因素的功能。然后，我们深入研究了依赖于上下文的鉴定和功能表征，对驱动器非整倍体的驱动基因进行了研究，并检查了新兴策略，以使用癌症基因组数据和癌症模型来揭示这些驱动基因。最后，我们通过利用这些常见的遗传改变的功能后果来探索靶向癌症驱动型非整倍性的机会。
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.