Gastroenterology and Hepatology Institute, Meir Medical Center, Kfar Saba, Israel.
Gene. 2013 Oct 25;529(2):245-9. doi: 10.1016/j.gene.2013.07.098. Epub 2013 Aug 8.
Primary sclerosing cholangitis (PSC) is a chronic cholestatic disorder that involves inflammatory and fibrotic changes in the bile ducts. Up to 80% of patients have concomitant inflammatory bowel disease (IBD) with colitis. PSC patients are predisposed to develop hepatobiliary, colonic and other extrahepatic malignancies, probably related to inflammatory processes that might promote carcinogenesis. Telomerase is an enzyme complex that lengthens telomeres and has enhanced expression in numerous malignancies. In this study, we evaluated the TERC gene copy number, the proportion of cells in senescence and the amount of fragmentation in the senescent state.
Fluorescence in situ hybridization (FISH) for the TERC gene was applied to lymphocytes retrieved from PSC (N=19), colitis (N=20) and healthy control patients (N=20) to determine the TERC copy number. On the same FISH slides, cells stained with DAPI were also analyzed for senescence-associated heterochromatin foci (SAHF) status, including the number of cells with fragments and the number of SAHF fragments in each cell.
A higher TERC gene copy number was observed in cells from PSC patients compared to colitis and control group patients. It was also higher in the colitis than in the control group. Significantly more cells in the senescent state and more fragmentation in each cell were observed in the PSC group compared to colitis and control groups.
The TERC gene copy number and the number of cells in the senescent state were increased in PSC patients compared to the colitis and control groups. These findings are probably related to the genetic instability parameters that reflect the higher tendency of this patient group to develop malignancies.
原发性硬化性胆管炎（PSC）是一种慢性胆汁淤积性疾病，涉及胆管的炎症和纤维化变化。多达 80%的患者伴有炎症性肠病（IBD）和结肠炎。PSC 患者易发生肝胆、结肠和其他肝外恶性肿瘤，可能与促进癌变的炎症过程有关。端粒酶是一种酶复合物，可延长端粒，在许多恶性肿瘤中表达增强。在这项研究中，我们评估了 TERC 基因拷贝数、衰老细胞比例和衰老状态下的片段数量。
应用荧光原位杂交（FISH）检测从 PSC（N=19）、结肠炎（N=20）和健康对照组患者（N=20）中提取的淋巴细胞的 TERC 基因拷贝数。在同一 FISH 载玻片上，还分析了用 DAPI 染色的细胞衰老相关异染色质焦点（SAHF）状态，包括具有片段的细胞数量和每个细胞中的 SAHF 片段数量。
与结肠炎和对照组患者相比，PSC 患者的细胞 TERC 基因拷贝数更高。与对照组相比，结肠炎患者的 TERC 基因拷贝数也更高。与结肠炎和对照组相比，PSC 组中更多的细胞处于衰老状态，每个细胞中的片段更多。
与结肠炎和对照组相比，PSC 患者的 TERC 基因拷贝数和衰老细胞数量增加。这些发现可能与反映该患者组发生恶性肿瘤倾向较高的遗传不稳定性参数有关。
