Division of Oncology, Department of Medicine, Washington University School of Medicine, 660 S. Euclid Avenue, Campus Box 8007, Saint Louis, MO 63110, USA.
Best Pract Res Clin Haematol. 2012 Dec;25(4):409-14. doi: 10.1016/j.beha.2012.10.002. Epub 2012 Oct 23.
In the past decade, a series of technological advances have revolutionized our ability to interrogate cancer genomes, culminating in whole-genome sequencing, which provides genome-wide coverage at a single base-pair resolution. To date, the tumor genome has been sequenced in nearly 40 cases of acute myeloid leukemia (AML). On average, each AML genome contains approximately 400 mutations, including 6-26 coding mutations. The majority of these mutations are 'background' mutations that were acquired during normal aging of hematopoietic stem cells. Though comprehensively identifying 'driver' mutations remains a challenge, a number of novel driver mutations in AML have been identified through whole-genome sequencing. The digital nature of next-generation sequencing has revealed clonal heterogeneity in the majority of AML at diagnosis. Importantly, in some cases, a minor subclone contributed to relapse, suggesting the strategies to assess clonal heterogeneity are needed to optimize therapy. As sequencing technologies improve and costs decrease, it is likely that whole-genome sequencing of cancer cells will become commonplace in the diagnostic work-up of patients with AML and other cancers.
在过去的十年中，一系列技术进步彻底改变了我们对癌症基因组进行检测的能力，最终实现了全基因组测序，其能以单个碱基对的分辨率提供基因组范围的覆盖。迄今为止，已经对近 40 例急性髓系白血病 (AML) 患者的肿瘤基因组进行了测序。平均而言，每个 AML 基因组包含大约 400 个突变，包括 6-26 个编码突变。这些突变中的大多数是造血干细胞正常衰老过程中获得的“背景”突变。尽管全面识别“驱动”突变仍然是一个挑战，但通过全基因组测序已经鉴定出了 AML 中的一些新的驱动突变。下一代测序的数字化性质揭示了大多数 AML 在诊断时的克隆异质性。重要的是，在某些情况下，次要亚克隆导致复发，这表明需要评估克隆异质性的策略来优化治疗。随着测序技术的改进和成本的降低，对 AML 和其他癌症患者的癌细胞进行全基因组测序可能会成为常规诊断。
