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脓胸相关性淋巴瘤中的凝聚素突变与异常染色体结构

Condensin mutations and abnormal chromosomal structures in pyothorax-associated lymphoma.

作者信息

Ham Maria Francisca, Takakuwa Tetsuya, Rahadiani Nur, Tresnasari Kristianti, Nakajima Hiroo, Aozasa Katsuyuki

机构信息

Department of Pathology, Osaka University Graduate School of Medicine, Osaka, Japan.

出版信息

Cancer Sci. 2007 Jul;98(7):1041-7. doi: 10.1111/j.1349-7006.2007.00500.x. Epub 2007 May 4.

Abstract

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.

摘要

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。

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