Cottliar A S, Fundia A F, Morán C, Sosa E, Geldern P, Gómez J C, Chopita N, Slavutsky I R
Dept. de Genética, Instituto de Investigaciones Hematológicas Mariano R. Castex, Academia Nacional de Medicina, Buenos Aires, Argentina.
J Exp Clin Cancer Res. 2000 Dec;19(4):513-7.
In the current study we analyzed chromosome instability on peripheral blood lymphocytes cultured from 7 untreated patients with chronic pancreatitis (CP) by assessing telomeric associations (TAS), chromosome aberrations (CA) and sister chromatid exchanges (SCE). Seven healthy individuals were also analyzed. Mean frequencies of TAS were significantly higher in CP patients (X +/- SE: 11.00 +/- 2.37) compared to controls (1.00 +/- 0.30) (p<0.001). Chromosomes preferentially involved in TAS were: 9, 20, 16 and 21, being the most affected arms: 9p, 20q, 16p, 9q and 21q. All these terminal bands were coincident with cancer breakpoints (p<0.03), two of them (40%) were specifically associated to pancreatic carcinoma rearrangements. Three bands (60%) were coincident with oncogene location. The mean frequency of CA was significantly higher in patients (3.88 +/- 0.80) compared to controls (0.63 +/- 0.49) (p<0.001). Chromosomes 1, 2 and 13 were the most damaged. No specifically affected breakpoints were found. SCE analysis showed higher levels in patients (8.33 +/- 0.70) than in controls (6.62 +/- 0.34) (p<0.025), but no differences were observed in cell cycle kinetics. Our results clearly indicate that CP patients exhibit chromosome instability, showing the presence of an unstable genome that could be related to the cancer development observed in this disease.
在本研究中，我们通过评估端粒联合（TAS）、染色体畸变（CA）和姐妹染色单体交换（SCE），分析了7例未经治疗的慢性胰腺炎（CP）患者外周血淋巴细胞的染色体不稳定性。同时也分析了7名健康个体。与对照组（1.00±0.30）相比，CP患者的TAS平均频率显著更高（X±SE：11.00±2.37）（p<0.001）。优先参与TAS的染色体为：9、20、16和21，受影响最严重的臂为：9p、20q、16p、9q和21q。所有这些末端带均与癌症断点一致（p<0.03），其中两条（40%）与胰腺癌重排特异性相关。三条带（60%）与癌基因位置一致。患者的CA平均频率（3.88±0.80）显著高于对照组（0.63±0.49）（p<0.001）。1、2和13号染色体受损最严重。未发现特异性受影响的断点。SCE分析显示患者水平（8.33±0.70）高于对照组（6.62±0.34）（p<0.025），但在细胞周期动力学方面未观察到差异。我们的结果清楚地表明，CP患者表现出染色体不稳定性，显示出存在不稳定的基因组，这可能与该疾病中观察到的癌症发展有关。
