透明细胞肾细胞癌（ccRCC）是肾癌最常见的形式，但缺乏对其基因组图谱的全面描述。我们报告了参与 100,000 基因组计划的 778 名 ccRCC 患者的全基因组测序，提供了 ccRCC 体细胞突变情况的详细描述。我们确定了候选驱动基因，并强调了表观遗传调控在 ccRCC 中的主要作用，并强调了其他生物途径，扩大了治疗干预的机会。基因组特征鉴定出具有不同临床结果的患者；较高数量的结构拷贝数改变与较差的预后相关，而VHL突变与较好的预后独立相关。较高的 T 细胞浸润与较好的总体生存率相关，并且基因预测的免疫逃避并不常见，这一观察结果支持了免疫治疗的基本原理。这些发现应为 ccRCC 患者的个性化监测和治疗策略提供信息。© 2024。作者。

Clear cell renal cell carcinoma (ccRCC) is the most common form of kidney cancer, but a comprehensive description of its genomic landscape is lacking. We report the whole genome sequencing of 778 ccRCC patients enrolled in the 100,000 Genomes Project, providing for a detailed description of the somatic mutational landscape of ccRCC. We identify candidate driver genes, which as well as emphasising the major role of epigenetic regulation in ccRCC highlight additional biological pathways extending opportunities for therapeutic interventions. Genomic characterisation identified patients with divergent clinical outcome; higher number of structural copy number alterations associated with poorer prognosis, whereas VHL mutations were independently associated with a better prognosis. The observations that higher T-cell infiltration is associated with better overall survival and that genetically predicted immune evasion is not common supports the rationale for immunotherapy. These findings should inform personalised surveillance and treatment strategies for ccRCC patients.© 2024. The Author(s).