Barcelona Supercomputing Center (BSC), Barcelona, Spain.
Josep Carreras Leukaemia Research Institute (IJC), Badalona, Spain.
FEBS Lett. 2020 Dec;594(24):4233-4246. doi: 10.1002/1873-3468.13781. Epub 2020 Apr 28.
One of the key challenges of cancer biology is to catalogue and understand the somatic genomic alterations leading to cancer. Although alternative definitions and search methods have been developed to identify cancer driver genes and mutations, analyses of thousands of cancer genomes return a remarkably similar catalogue of around 300 genes that are mutated in at least one cancer type. Yet, many features of these genes and their role in cancer remain unclear, first and foremost when a somatic mutation is truly oncogenic. In this review, we first summarize some of the recent efforts in completing the catalogue of cancer driver genes. Then, we give an overview of different aspects that influence the oncogenicity of somatic mutations in the core cancer driver genes, including their interactions with the germline genome, other cancer driver mutations, the immune system, or their potential role in healthy tissues. In the coming years, this research holds promise to illuminate how, when, and why cancer driver genes and mutations are really drivers, and thereby move personalized cancer medicine and targeted therapies forward.
癌症生物学的主要挑战之一是对导致癌症的体细胞基因组改变进行编目和理解。虽然已经开发了替代的定义和搜索方法来识别癌症驱动基因和突变，但对数千个癌症基因组的分析返回了一个惊人相似的目录，其中约有 300 个基因在至少一种癌症类型中发生了突变。然而，这些基因的许多特征及其在癌症中的作用仍然不清楚，首先是当体细胞突变真正致癌时。在这篇综述中，我们首先总结了完成癌症驱动基因目录的一些最新努力。然后，我们概述了影响核心癌症驱动基因中体细胞突变致癌性的不同方面，包括它们与种系基因组、其他癌症驱动突变、免疫系统的相互作用，或它们在健康组织中的潜在作用。在未来几年，这项研究有望阐明癌症驱动基因和突变如何、何时以及为何真正成为驱动因素，从而推动个性化癌症医学和靶向治疗向前发展。
