Telomere shortening and telomerase reactivation in dysplastic nodules of human hepatocarcinogenesis.
OBJECTIVE
The maintenance of telomere with telomerase reactivation, vital for carcinogenesis, was studied in human multistep hepatocarcinogenesis for the characterization of borderline lesions.


METHODS
The terminal restriction fragment length (TRFL) and telomerase activity (TA) were examined in 3 chronic hepatitis (CH), 10 cirrhosis, 7 large regenerative nodules (LRNs), 30 low grade dysplastic nodules (LGDNs), 6 high grade DNs (HGDNs), 3 DNs with hepatocellular carcinoma (HCC) foci, 11 HCCs, and 4 normal livers by Southern hybridization and TRAPeze Elisa telomerase detection.


RESULTS
The TRFL and TA showed significant differences between the LGDNs and HGDNs. Most LGDNs had similar levels of TRFL and TA to those of the CH, cirrhosis and LRNs, however, 17% of LGDNs revealed shortening of telomeres up to the levels of HGDNs and 7% of LGDNs showed high levels of TA. The levels of TRFL and TA in HGDNs showed no significant differences from those of DNs with HCC foci and HCCs.


CONCLUSIONS
The shortening of telomeres and reactivation of telomerase occur in the DNs during the early stages of hepatocarcinogenesis, with a significant change in the transition of LGDNs to HGDNs. The characteristics of HGDNs are considered to be closer to those of HCCs.
Oh
Bong-Kyeong
BK
Department of Pathology and Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, CPO Box 8044, Seoul, South Korea.
Jo Chae
Kwang
K
Park
Chanil
C
Kim
Kyungsik
K
Jung Lee
Woo
W
Han
Kwang-hyub
KH
Nyun Park
Young
Y
D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000209:etiology* / Q000473:pathology; D016022:Case-Control Studies; D002908:Chronic Disease; D004789:Enzyme Activation; D005260:Female; D006505:Hepatitis / Q000150:complications / Q000201:enzymology / Q000235:genetics; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications / Q000201:enzymology / Q000235:genetics; D008107:Liver Diseases / Q000150:complications / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D008113:Liver Neoplasms / Q000209:etiology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length; D011230:Precancerous Conditions / Q000150:complications / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D019098:Telomerase / Q000378:metabolism*; D016615:Telomere / Q000235:genetics*
D019098:Telomerase