Telomere Shortening Correlates With Increasing Aneuploidy... : Hepatology (original) (raw)

Rapid Communication

Telomere Shortening Correlates With Increasing Aneuploidy of Chromosome 8 in Human Hepatocellular Carcinoma*

Plentz, Ruben R.1; Schlegelberger, Brigitte2; Flemming, Peer3; Gebel, Michael1; Kreipe, Hans3; Manns, Michael P.1; Rudolph, Lenhard K.1†‡; Wilkens, Ludwig2,3¶∥

1 Department of Gastroenterology, Hepatology and Endocrinology, Medical School of Hannover, Germany

2 Institute of Cell and Molecular Pathology, Medical School of Hannover, Germany

3 Department of Pathology, Medical School of Hannover, Germany

† Department of Gastroenterology, Hepatology, and Endocrinology, Medical School of Hannover, Carl-Neuberg-Str. 1, 30625 Hannover, Germany

¶ Institute of Cell and Molecular Pathology and Department of Pathology, Medical School of Hannover, Carl-Neuberg-Str. 1, 30625 Hannover, Germany

Email:[email protected]

Received 23 April 2005; Accepted 28 June 2005

Published online in Wiley InterScience (www.interscience.wiley.com).

*Potential conflict of interest: Nothing to report.

‡fax: (49) 511-532-2021

∥fax: (49) 511-532-4521

Abstract

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. (Hepatology 2005;42:522–526.)