英国癌症研究所Richard Houlston课题组在研究中取得进展。他们通过对10,478个癌症基因组进行分析，确定了候选诱导基因和精准肿瘤学的潜在靶点。相关论文发表在2024年6月18日出版的《自然-遗传学》杂志上。

肿瘤基因组图谱分析越来越被视为指导癌症治疗的先决条件。为了探索全基因组测序（WGS）在癌症精准治疗方面的价值，研究人员分析了英国十万基因组计划（UK100,000 Genomes Project）中10,478名患者的全基因组测序数据，包涵35种癌症类型。研究确定了330个候选驱动基因，其中74个为新发现的癌症驱动基因。

研究人员估计在所研究的患者中，约有55%的患者携带至少一种与临床相关的突变，这些突变可预测对某些治疗的敏感性或耐药性，或预测是否具有临床试验资格。通过对癌症突变进行计算化学基因组分析，研究发现了更多化合物的靶点，这些靶点对未来的临床试验具有吸引力。这项研究是迄今为止在现实世界中识别癌症驱动基因，并评估其对精准肿瘤学影响最全面的工作之一。

附：英文原文

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

Author: Kinnersley, Ben, Sud, Amit, Everall, Andrew, Cornish, Alex J., Chubb, Daniel, Culliford, Richard, Gruber, Andreas J., Lrkeryd, Adrian, Mitsopoulos, Costas, Wedge, David, Houlston, Richard

Issue&Volume: 2024-06-18

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.

DOI: 10.1038/s41588-024-01785-9

Source: https://www.nature.com/articles/s41588-024-01785-9