Abstract
BACKGROUND
Despite the recent discovery of interchromosomal telomere length variation, a role for heterogeneity in telomere maintenance has yet to be established. This study investigated the significance of telomere length variation between chromosomes with respect to the association of cancer progression and telomere length regulation.
METHODS
Terminal restriction fragment (TRF) was evaluated in 20 surgically resected hepatocellular carcinoma specimens (HCC), corresponding noncancerous liver tissue specimens (NCL), and in 10 liver tissue specimens with chronic liver diseases devoid of cancer (DOC). Average TRF length (TRFβA) was defined as the point of maximum intensity. Shorter and longer TRF lengths (TRFβS and TRFβL) were defined as the length above which 90% of TRF distribution was involved. A ratio, (TRFβLβTRFβS)/TRFβA, was defined as telomere length dispersion.
RESULTS
The dispersion was significantly larger in HCC than in NCL specimens (P = 0.012) and in NCL than in DOC (P = 0.048). TRFβA and TRFβS were significantly shorter in HCC than in NCL (P = 0.0026, P = 0.0010). In seven patients in whom HCC recurred within 1 year, TRFβA and TRFβS were significantly shorter than in 10 patients in whom recurrence occurred after 1 year (P = 0.018, P = 0.0097). Telomeric repeat binding factor 1 was upβregulated in HCC with elongated TRFβL, whereas expression of human telomerase reverse transcriptase was greater in HCC with a shorter TRFβS.
CONCLUSIONS
These results suggest that telomere length varied through chronic liver diseases by preferentially increasing shorter telomeres, whose length is a good indicator for malignant potential of HCC. Telomere length variation may be a crucial code in telomere maintenance through hepatocarcinogenesis. Cancer 2003;98:110β8. Β© 2003 American Cancer Society.
DOI 10.1002/cncr.11428