Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada.
National Library of Medicine, National Institutes of Health (NIH), Bethesda, MD, USA.
Trends Mol Med. 2023 Jul;29(7):554-566. doi: 10.1016/j.molmed.2023.03.007. Epub 2023 Apr 17.
Cancer cells accumulate many genetic alterations throughout their lifetime, but only a few of them drive cancer progression, termed driver mutations. Driver mutations may vary between cancer types and patients, can remain latent for a long time and become drivers at particular cancer stages, or may drive oncogenesis only in conjunction with other mutations. The high mutational, biochemical, and histological tumor heterogeneity makes driver mutation identification very challenging. In this review we summarize recent efforts to identify driver mutations in cancer and annotate their effects. We underline the success of computational methods to predict driver mutations in finding novel cancer biomarkers, including in circulating tumor DNA (ctDNA). We also report on the boundaries of their applicability in clinical research.
癌细胞在其一生中会积累许多遗传改变，但只有其中少数几个会推动癌症的进展，这些改变被称为驱动突变。驱动突变可能因癌症类型和患者而异，它们可能长期潜伏，然后在特定的癌症阶段成为驱动因素，或者可能仅与其他突变一起驱动肿瘤发生。由于肿瘤的高突变、生化和组织学异质性，使得驱动突变的识别极具挑战性。在这篇综述中，我们总结了最近在癌症中识别驱动突变并对其作用进行注释的努力。我们强调了计算方法在预测驱动突变以寻找新的癌症生物标志物方面的成功，包括循环肿瘤 DNA（ctDNA）中的应用。我们还报告了它们在临床研究中的应用局限性。
