Telomere shortening correlates with increasing aneuploidy of chromosome 8 in human hepatocellular carcinoma
Telomere shortening correlates with increasing aneuploidy of chromosome 8 in human hepatocellular carcinoma
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DOI：
10.1002/hep.20847
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发表时间：
2005-09-01
期刊：
影响因子：
13.5
通讯作者：
Wilkens, L
中科院分区：
文献类型：
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作者：
Plentz, RR;Schlegelberger, B;Wilkens, L
染色体不稳定性 (CIN) 会导致人类肝细胞癌 (HCC) 中非整倍性和染色体畸变的增加。端粒缩短似乎是促进 CIN 发展的一种机制。端粒缩短是否与某种癌症的特定基因变化相关尚待确定。在我们最近的研究中，我们在细胞水平上结合了肝细胞端粒荧光强度 (TFI) 和 8 号染色体拷贝数（肝细胞癌 (HCC) 标志性染色体改变之一）的分析。我们研究了 15 个非整倍体 HCC 的细胞学细针活检和 5 个无癌症尸体肝脏的触摸指纹。肝细胞特异性TFI和8号染色体着丝粒特异性探针的测量均通过定量荧光原位杂交（qFISH）或FISH进行。两种方法的联合分析 (coFISH) 可以在单细胞水平上测量端粒长度和 8 号染色体拷贝数。我们观察到，在细胞水平上，端粒缩短与肝癌中 8 号染色体拷贝数的增加显着相关。在每个核 5 号染色体拷贝的水平之上，没有发现端粒进一步缩短，表明端粒在非整倍性的这个阶段已经达到了非常短的长度。总之，我们的研究提供了直接证据，表明端粒缩短与人类肝癌的特定基因改变特征有关。
Chromosomal instability (CIN) leads to an increase in aneuploidy and chromosomal aberrations in human hepatocellular carcinoma (HCC). Telomere shortening appears as one mechanism fostering the development of CIN. Whether telomere shortening correlates to specific genetic changes that characterize a certain type of cancer has yet to be established. In our recent study, we combined on a cellular level the analysis of hepatocellular telomere fluorescent intensity (TFI) and copy number of chromosome 8-one of the hallmark chromosomal alterations in hepatocellular carcinoma (HCC). We investigated 15 cytological fine-needle biopsies of aneuploid HCC and 5 touch prints of cadaver livers without cancer. Hepatocyte-specific TFI and the measurement of centromere-specific probe for chromosome 8 were both performed by quantitative fluorescence in situ hybridization (qFISH) or FISH. Combined analysis of both methods (coFISH) allowed measurement of telomere length and chromosome 8 copy number on a single cell level. We observed that telomere shortening correlates significantly with increasing copy number of chromosome 8 in HCC on the cellular level. Above the level of 5 copies of chromosome 8 per nucleus, no further shortening of telomeres was found, indicating that telomeres had reached a critically short length at this stage of aneuploidy. In conclusion, our study gives direct evidence that telomere shortening is linked to a specific genetic alteration characteristic for human HCC.