Ham Maria Francisca, Takakuwa Tetsuya, Rahadiani Nur, Tresnasari Kristianti, Nakajima Hiroo, Aozasa Katsuyuki
Department of Pathology, Osaka University Graduate School of Medicine, Osaka, Japan.
Cancer Sci. 2007 Jul;98(7):1041-7. doi: 10.1111/j.1349-7006.2007.00500.x. Epub 2007 May 4.
Transfer of genetic information during mitosis is accurately conducted by proper condensation and segregation of chromosomes, for which condensins play a central role. Both condensin I and II have common structural maintenance of chromosomes subunits, named hCAP-C and hCAP-E. Pyothorax-associated lymphoma (PAL) is a non-Hodgkin's lymphoma developing in the pleural cavity of patients with long-standing pyothorax. Mutations of hCAP-C and hCAP-E were investigated in 24 leukemia-lymphoma cell lines including eight PAL cell lines, and their influences in chromosome morphology were evaluated. Heterozygous point mutations within hCAP-C were found in two PAL cell lines and corresponding tumor samples (OPL-3 and OPL-7). Deletion of exon 24 within hCAP-E and a point mutation at the donor splice site of intron 24 were detected in OPL-5 and original tumor samples. OPL-5 showed an extensive reduction in expression of not only hCAP-E but also hCAP-C proteins. OPL-5 occasionally showed the chromosome bridge in anaphase and telophase, indicating that segregation is not accurate. OPL-7 showed reduced hCAP-C protein expression, abnormality in chromosome length and width, and abnormal aggregates of hCAP-C protein. These findings indicated that condensin gene alteration might play a role in genome instability, which accelerates the accumulation of other gene alterations in PAL.
在有丝分裂过程中,遗传信息的传递通过染色体的适当凝聚和分离得以准确进行,凝聚素在其中发挥着核心作用。凝聚素I和凝聚素II都有共同的染色体结构维持亚基,即hCAP-C和hCAP-E。脓胸相关性淋巴瘤(PAL)是一种在长期脓胸患者胸腔中发生的非霍奇金淋巴瘤。我们在包括8个PAL细胞系在内的24个白血病-淋巴瘤细胞系中研究了hCAP-C和hCAP-E的突变情况,并评估了它们对染色体形态的影响。在两个PAL细胞系以及相应的肿瘤样本(OPL-3和OPL-7)中发现了hCAP-C内的杂合点突变。在OPL-5及其原始肿瘤样本中检测到hCAP-E外显子24的缺失以及内含子24供体剪接位点的一个点突变。OPL-5不仅显示hCAP-E蛋白表达大幅降低,hCAP-C蛋白表达也降低。OPL-5在后期和末期偶尔会出现染色体桥,表明分离不准确。OPL-7显示hCAP-C蛋白表达降低、染色体长度和宽度异常以及hCAP-C蛋白异常聚集。这些发现表明凝聚素基因改变可能在基因组不稳定中起作用,这加速了PAL中其他基因改变的积累。