荷兰乌得勒支大学医学中心Edwin Cuppen研究团队绘制了转移性实体肿瘤的泛肿瘤全基因组图谱。该研究于2019年10月23日在线发表于国际一流学术期刊《自然》。

研究人员报道了目前最大的转移性实体瘤基因组泛肿瘤研究，包括对2520对肿瘤和正常组织的全基因组测序数据，分别在中位深度106倍和38倍处进行了分析，并研究了超过7000万种体细胞变体。转移性病变的特征性突变差异很大，其突变反映了原发性肿瘤的类型，并且全基因组重复事件发生率很高（56％）。单个转移灶相对均质，绝大多数（96％）驱动基因突变是克隆性的，高达80％的肿瘤抑制基因通过不同的突变机制双等位失活。

尽管转移性肿瘤基因组显示出与原发性肿瘤相似的突变态势和驱动基因，但研究人员发现可能对个别患者的治疗反应或耐药性有贡献的特征。研究人员使用了一种方法来回顾临床相关的关联及其潜在的可操作性。对于62％的患者，研究人员确定了可以用于将患者分层以进行已批准或正在临床治疗的基因变异。这证明了全面基因组肿瘤图谱对癌症精确医疗的重要性。

据悉，转移性癌症是主要的死亡原因，并且与不良的治疗效果有关。人们需要更好地了解晚期癌症的特征，以帮助适应个性化治疗、减少过度治疗并改善预后。

附：英文原文

Title: Pan-cancer whole-genome analyses of metastatic solid tumours

Author: Peter Priestley, Jonathan Baber, Martijn P. Lolkema, Neeltje Steeghs, Ewart de Bruijn, Charles Shale, Korneel Duyvesteyn, Susan Haidari, Arne van Hoeck, Wendy Onstenk, Paul Roepman, Mircea Voda, Haiko J. Bloemendal, Vivianne C. G. Tjan-Heijnen, Carla M. L. van Herpen, Mariette Labots, Petronella O. Witteveen, Egbert F. Smit, Stefan Sleijfer, Emile E. Voest, Edwin Cuppen

Issue&Volume: 2019-10-23

Abstract: Metastatic cancer is a major cause of death and is associated with poor treatment efficacy. A better understanding of the characteristics of late-stage cancer is required to help adapt personalized treatments, reduce overtreatment and improve outcomes. Here we describe the largest, to our knowledge, pan-cancer study of metastatic solid tumour genomes, including whole-genome sequencing data for 2,520 pairs of tumour and normal tissue, analysed at median depths of 106× and 38×, respectively, and surveying more than 70 million somatic variants. The characteristic mutations of metastatic lesions varied widely, with mutations that reflect those of the primary tumour types, and with high rates of whole-genome duplication events (56%). Individual metastatic lesions were relatively homogeneous, with the vast majority (96%) of driver mutations being clonal and up to 80% of tumour-suppressor genes being inactivated bi-allelically by different mutational mechanisms. Although metastatic tumour genomes showed similar mutational landscape and driver genes to primary tumours, we find characteristics that could contribute to responsiveness to therapy or resistance in individual patients. We implement an approach for the review of clinically relevant associations and their potential for actionability. For 62% of patients, we identify genetic variants that may be used to stratify patients towards therapies that either have been approved or are in clinical trials. This demonstrates the importance of comprehensive genomic tumour profiling for precision medicine in cancer.

DOI: 10.1038/s41586-019-1689-y

Source: https://www.nature.com/articles/s41586-019-1689-y