Hepatocyte telomere shortening of primary HCC correlates with increasing aneuploidy of chromosome 8

Introduction: Hepatocellular carcinoma (HCC) is a common malignant tumor world-wide. It is well known that chromosomal instability (CIN) leads to an increase of aneuploidy in human HCC with an increased rate of chromosomal aberrations. In our study we for the first time combined on a cellular level the analysis of hepatocellular telomere fluorescent intensity (TFI) and copy number of chromosme 8– one of the hallmark chromosomal alterations in HCC.

Patient and Methods: We investigated 15 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) respectively FISH:

Results: Comparative analysis of telomere length and chromosome 8 copy numbers showed significantly shorter telomers in hepatocytes of HCC with increased chromosome 8 copy number.There was a significant correlation between shorter telomeres and increasing chromosome 8 copy number. However, above the level of 5 copies of chromosome 8 per nuclei no further shortening of telomeres was found indicating that telomeres had reached a critically short length. Compared to the group of HCC no aneuploidy of chromosome 8 was found in the control samples, which had significantly longer telomeres compared to the HCC.

Conclusions: Our study gives first direct evidence that telomere shortening is linked to a specific genetic alteration characteristic for human HCC.

Keywords: CIN, HCC, Ploidy, q-FISH