Cottliar A, Fundia A, Boerr L, Sambuelli A, Negreira S, Gil A, Gómez J C, Chopita N, Bernedo A, Slavutsky I
Departamento de Genética, Instituto de Investigaciones Hematológicas Mariano R Castex, Academia Nacional de Medicina, Buenos Aires, Argentina.
Am J Gastroenterol. 2000 Sep;95(9):2301-7. doi: 10.1111/j.1572-0241.2000.02315.x.
Chromosome instability provides a predisposing background to malignancy, contributing to the crucial genetic changes in multistep carcinogenesis. The aim of this work was to analyze chromosome instability in patients with ulcerative colitis (UC) to achieve a better understanding of the increased risk for colorectal cancer.
Peripheral blood lymphocyte cultures from 20 untreated UC patients and 24 controls were used to study chromosome instability by assessing telomeric associations (TAS), chromosome aberrations (CA), and sister chromatid exchanges (SCE).
Mean frequencies of TAS and CA were significantly increased in UC patients compared to controls (p < 0.001). Chromosomes 10, 11, 21, 16, and 19 were the most frequently involved in TAS. A total of 104 CA clustered in 66 breakpoints could be exactly localized. Seven nonrandom bands significantly affected in UC patients were found (p < 0.004), showing a significant correlation with the location of cancer breakpoints (p < 0.003), particularly with colorectal carcinoma rearrangements. SCE analysis showed higher levels in patients compared to controls (p < 0.006), but no differences were observed in cell cycle kinetics.
Our results demonstrate the presence of an unstable genome in UC patients that could be related to the cancer development observed in this disease.
染色体不稳定为恶性肿瘤提供了一个易患背景，在多步骤致癌过程中促成关键的基因变化。这项工作的目的是分析溃疡性结肠炎（UC）患者的染色体不稳定情况，以便更好地理解其患结直肠癌风险增加的原因。
采用20例未经治疗的UC患者和24例对照的外周血淋巴细胞培养物，通过评估端粒联合（TAS）、染色体畸变（CA）和姐妹染色单体交换（SCE）来研究染色体不稳定情况。
与对照组相比，UC患者的TAS和CA平均频率显著增加（p < 0.001）。10号、11号、21号、16号和19号染色体是TAS中最常受累的染色体。总共104个CA聚集在66个断点处，可以精确定位。在UC患者中发现7条受显著影响的非随机带（p < 0.004），与癌症断点的位置有显著相关性（p < 0.003），特别是与结直肠癌重排相关。SCE分析显示患者水平高于对照组（p < 0.006），但在细胞周期动力学方面未观察到差异。
我们的结果表明UC患者存在不稳定基因组，这可能与该疾病中观察到的癌症发生有关。
