Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
J Clin Oncol. 2013 May 20;31(15):1885-92. doi: 10.1200/JCO.2013.48.7447. Epub 2013 Apr 15.
The use of candidate gene and genome-wide discovery studies in the last several years has led to an expansion of our knowledge of the spectrum of recurrent, somatic disease alleles, which contribute to the pathogenesis of hematologic malignancies. Notably, these studies have also begun to fundamentally change our ability to develop informative prognostic schema that inform outcome and therapeutic response, yielding substantive insights into mechanisms of hematopoietic transformation in different tissue compartments. Although these studies have already had important biologic and translational impact, significant challenges remain in systematically applying these findings to clinical decision making and in implementing new technologies for genetic analysis into clinical practice to inform real-time decision making. Here, we review recent major genetic advances in myeloid and lymphoid malignancies, the impact of these findings on prognostic models, our understanding of disease initiation and evolution, and the implication of genomic discoveries on clinical decision making. Finally, we discuss general concepts in genetic modeling and the current state-of-the-art technology used in genetic investigation.
近年来,候选基因和全基因组发现研究的应用使得我们对导致血液系统恶性肿瘤发病机制的复发性体细胞疾病等位基因谱的认识得到了扩展。值得注意的是,这些研究也开始从根本上改变我们开发信息丰富的预后方案的能力,从而为不同组织隔室中的造血转化机制提供实质性的见解。尽管这些研究已经具有重要的生物学和转化影响,但在系统地将这些发现应用于临床决策制定以及将新的遗传分析技术应用于临床实践以实时决策方面仍然存在重大挑战。在这里,我们回顾了髓系和淋巴系恶性肿瘤的最新重大遗传进展,这些发现对预后模型的影响,我们对疾病起始和演变的理解,以及基因组发现对临床决策的影响。最后,我们讨论了遗传建模的一般概念和遗传研究中当前使用的最先进技术。