Strefford Jonathan C
Cancer Genomics, Academic Unit of Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
Br J Haematol. 2015 Apr;169(1):14-31. doi: 10.1111/bjh.13254. Epub 2014 Dec 11.
Chronic lymphocytic leukaemia (CLL) remains at the forefront of the genetic analysis of human tumours, principally due its prevalence, protracted natural history and accessibility to suitable material for analysis. With the application of high-throughput genetic technologies, we have an unbridled view of the architecture of the CLL genome, including a comprehensive description of the copy number and mutational landscape of the disease, a detailed picture of clonal evolution during pathogenesis, and the molecular mechanisms that drive genomic instability and therapeutic resistance. This work has nuanced the prognostic importance of established copy number alterations, and identified novel prognostically relevant gene mutations that function within biological pathways that are attractive treatment targets. Herein, an overview of recent genomic discoveries will be reviewed, with associated biological and clinical implications, and a view into how clinical implementation may be facilitated.
慢性淋巴细胞白血病(CLL)一直处于人类肿瘤基因分析的前沿,这主要归功于其高发性、漫长的自然病程以及易于获取适合分析的样本。随着高通量基因技术的应用,我们得以全面了解CLL基因组的结构,包括对该疾病的拷贝数和突变图谱的详尽描述、发病机制中克隆进化的详细情况,以及驱动基因组不稳定和治疗耐药性的分子机制。这项工作细化了已确定的拷贝数改变的预后重要性,并识别出了在具有吸引力的治疗靶点的生物学途径中发挥作用的、与预后相关的新基因突变。在此,将对近期的基因组学发现进行综述,并探讨其相关的生物学和临床意义,以及如何推动临床应用。