Mullally Ann, Ritz Jerome
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Blood. 2007 Feb 15;109(4):1355-62. doi: 10.1182/blood-2006-06-030858. Epub 2006 Sep 28.
The last 2 years have seen much excitement in the field of genetics with the identification of a formerly unappreciated level of "structural variation" within the normal human genome. Genetic structural variants include deletions, duplications, and inversions in addition to the recently discovered, copy number variants. Single nucleotide polymorphisms are the most extensively evaluated variant within the genome to date. Combining our knowledge from these studies with our rapidly accumulating understanding of structural variants, it is apparent that the extent of genetic dissimilarity between any 2 individuals is considerable and much greater than that which was previously recognized. Clearly, this more diverse view of the genome has significant implications for allogeneic hematopoietic stem cell transplantation, not least in the generation of transplant antigens but also in terms of individual susceptibility to transplant-related toxicities. With advances in DNA sequencing technology we now have the capacity to perform genome-wide analysis in a high throughput fashion, permitting a detailed genetic analysis of patient and donor prior to transplantation. Understanding the significance of this additional genetic information and applying it in a clinically meaningful way will be one of the challenges faced by transplant clinicians in the future.
在过去两年里，遗传学领域出现了诸多令人兴奋的进展，人们发现了正常人类基因组中以前未被重视的“结构变异”水平。除了最近发现的拷贝数变异外，遗传结构变异还包括缺失、重复和倒位。单核苷酸多态性是迄今为止基因组中评估最广泛的变异。将这些研究中的知识与我们对结构变异迅速积累的理解相结合，很明显，任何两个个体之间的遗传差异程度相当大，远大于之前所认识到的。显然，这种对基因组更为多样化的看法对异基因造血干细胞移植具有重大意义，这不仅体现在移植抗原的产生方面，还体现在个体对移植相关毒性的易感性方面。随着DNA测序技术的进步，我们现在有能力以高通量方式进行全基因组分析，从而在移植前对患者和供体进行详细的遗传分析。理解这些额外遗传信息的意义并以临床有意义的方式应用它，将是移植临床医生未来面临的挑战之一。
