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分析 10478 个癌症基因组，鉴定候选驱动基因和精准肿瘤学机会。

Analysis of 10,478 cancer genomes identifies candidate driver genes and opportunities for precision oncology.

机构信息

Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.

University College London Cancer Institute, University College London, London, UK.

出版信息

Nat Genet. 2024 Sep;56(9):1868-1877. doi: 10.1038/s41588-024-01785-9. Epub 2024 Jun 18.

DOI:10.1038/s41588-024-01785-9
PMID:38890488
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11387197/
Abstract

Tumor genomic profiling is increasingly seen as a prerequisite to guide the treatment of patients with cancer. To explore the value of whole-genome sequencing (WGS) in broadening the scope of cancers potentially amenable to a precision therapy, we analysed whole-genome sequencing data on 10,478 patients spanning 35 cancer types recruited to the UK 100,000 Genomes Project. We identified 330 candidate driver genes, including 74 that are new to any cancer. We estimate that approximately 55% of patients studied harbor at least one clinically relevant mutation, predicting either sensitivity or resistance to certain treatments or clinical trial eligibility. By performing computational chemogenomic analysis of cancer mutations we identify additional targets for compounds that represent attractive candidates for future clinical trials. This study represents one of the most comprehensive efforts thus far to identify cancer driver genes in the real world setting and assess their impact on informing precision oncology.

摘要

肿瘤基因组分析越来越被视为指导癌症患者治疗的前提。为了探索全基因组测序（WGS）在扩大潜在精准治疗癌症范围方面的价值，我们分析了英国 10 万基因组计划招募的 35 种癌症类型的 10478 名患者的全基因组测序数据。我们确定了 330 个候选驱动基因，其中包括 74 个是新的癌症基因。我们估计，大约 55%的研究患者至少携带一个具有临床意义的突变，这预示着对某些治疗方法或临床试验资格的敏感性或耐药性。通过对癌症突变进行计算化学基因组分析，我们确定了其他化合物的潜在靶点，这些化合物是未来临床试验的有吸引力的候选药物。这项研究是迄今为止在真实环境中识别癌症驱动基因并评估其对精准肿瘤学的影响的最全面的研究之一。

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