Division of Molecular Medicine, Department of Cancer Genetics, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
Int J Hematol. 2010 Sep;92(2):238-45. doi: 10.1007/s12185-010-0662-1. Epub 2010 Aug 27.
Chromosome translocations found in B cell lymphomas generate typical genome profiles that are characteristic of each disease entity. The mechanisms of lymphomagenesis have been investigated with respect to the involvement of deregulated genes in tumor development, as characterized by the promotion of cell proliferation and the blockage of cell differentiation and anti-apoptosis. It is now well known that chromosome translocation alone does not induce tumor formation. New technology such as array CGH and expression profiling introduced as a result of the human genome project introduced a new paradigm from which to understand the molecular mechanisms of lymphoma development. Analyses with this new technology revealed that genome profiles of disease entities are characteristic and differ from disease to disease, although the genome profile of each patient with the same disease entity varies significantly given the recurrent genetic alterations frequently found. These apparent paradoxical findings are likely to be the cause of heterogeneity of the clinicopathological features associated with the same disease entity. Based on these findings, the future prospect and direction of lymphoma research will be discussed.
在 B 细胞淋巴瘤中发现的染色体易位产生了每种疾病特有的典型基因组图谱。淋巴瘤发生的机制已经通过研究失调基因在肿瘤发展中的作用进行了研究,其特征是促进细胞增殖和阻止细胞分化和抗细胞凋亡。现在已经很清楚,染色体易位本身并不会诱导肿瘤形成。人类基因组计划带来的新技术,如 array CGH 和表达谱分析,引入了一种新的范例,从中可以了解淋巴瘤发展的分子机制。利用这项新技术进行的分析表明,疾病实体的基因组图谱具有特征性,并且彼此不同,尽管具有相同疾病实体的每个患者的基因组图谱因经常发现的反复遗传改变而有很大差异。这些明显的矛盾发现可能是导致与同一疾病实体相关的临床病理特征异质性的原因。基于这些发现,将讨论淋巴瘤研究的未来前景和方向。