Hepatocellular telomere shortening correlates with chromosomal instability and the development of human hepatoma
Hepatocellular telomere shortening correlates with chromosomal instability and the development of human hepatoma
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DOI：
10.1002/hep.20271
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发表时间：
2004-07-01
期刊：
影响因子：
13.5
通讯作者：
Rudolph, KL
中科院分区：
文献类型：
--
作者：
Plentz, RR;Caselitz, M;Rudolph, KL
端粒致癌假说表明，端粒缩短通过诱导染色体不稳定而致癌。为了验证这一假设是否适用于人类肝细胞癌，我们分析了39例肝硬变患者肝肿瘤细针活检细胞学涂片中肝细胞的端粒长度。肿瘤包括24个肝细胞癌和15个再生结节，经组织学和细胞学诊断。此外，我们还分析了另一组10例肝硬变患者中肝细胞的端粒长度及其周围非癌肝组织的端粒长度。肝细胞端粒长度分析与肿瘤病理及肿瘤倍体分级相关，采用细胞比色法进行分析。与再生结节或周围非癌肝组织相比，肝细胞癌中的肝细胞端粒明显缩短。肝细胞癌的肝细胞端粒缩短与患者的年龄无关。当比较肝细胞癌与再生结节或周围非癌肝组织时，个体样本的平均端粒长度没有重叠。在肝细胞癌组中，非整倍体肿瘤的肝细胞端粒明显短于二倍体肿瘤。综上所述，我们的数据表明，肿瘤起始的端粒假说适用于人类肝细胞癌，而特定细胞类型的端粒长度分析可能提示肝细胞癌发生的风险。
The telomere hypothesis of cancer initiation indicates that telomere shortening initiates cancer by induction of chromosomal instability. To test whether this hypothesis applies to human hepatocellular carcinoma (HCC), we analyzed the telomere length of hepatocytes in cytological smears of fine-needle biopsies of liver tumors from patients with cirrhosis (n = 39). The tumors consisted of 24 HCC and 15 regenerative nodules as diagnosed by combined histological and cytological diagnostics. In addition, we analyzed the telomere length of hepatocytes in HCC and surrounding noncancerous liver tissue within individual patients in another cohort of 10 patients with cirrhosis. Telomere length analysis of hepatocytes was correlated with tumor pathology and ploidy grade of the tumors, which was analyzed by cytophotometry. Telomeres were significantly shortened in hepatocytes of HCC compared to hepatocytes in regenerative nodules or surrounding noncancerous liver tissue. Hepatocyte telomere shortening in HCC was independent of the patient's age. There was no overlap in mean telomere lengths of individual samples when comparing HCC with regenerative nodules or noncancerous surrounding liver. Within the HCC group, telomeres were significantly shorter in hepatocytes of aneuploid tumors compared to diploid tumors. In conclusion, our data suggest that the telomere hypothesis of cancer initiation applies to human HCC and that cell type-specific telomere length analysis might indicate the risk of HCC development.