Microsatellite instability and mutations of E2F-4 in hepatocellular carcinoma from Korea

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Microsatellite instability and mutations of E2F-4 in hepatocellular carcinoma from Korea
Young Min Park; Jong Young Choi; Si Hyun Bae; Byoung Hun Byun; Byung Min Ahn; Boo Sung Kim; Deug Yong Shin
Bibliographic Citation
Hepatology Research, vol. 17, no. 2, pp. 102-111
Publication Year
It has been suggested that genetic changes in cancers are related to genomic instability. To evaluate a possible correlation between growth-regulatory genes and genomic instability in HCC, we investigated microsatellite instability and mutations of TGF-β type II receptor (TGF-β RII) and E2F-4 genes in each pair of tumor and surrounding nontumor liver tissues, collected from 19 patients with HCC. By the identification of mutations in six different genetic loci (D1S170, D2S123, D4S395, D13S126, D13S260, and D16S402), one or more alterations in microsatellite markers were identified in 13/19 (68%) hepatocellular carcinoma specimens. When two repeated sequences of TGF-β RII gene, poly(A)10 tract in exon 8 and poly(GT)3 tract in exon 9, were analyzed by polymerase chain reaction-single strand conformational polymorphism, none of the 19 hepatocellular carcinoma specimens showed mutations. When amplicons of poly(AGC)13 tract of E2F-4 were analyzed by cloning and automated sequencing, 5/19 (36%) hepatocellular carcinomas showed deletion mutation in one or two AGC repeats and such mutations were identified only among cases with microsatellite instability. These results suggest that both microsatellite instability and mutations of E2F-4 occur commonly in hepatocellular carcinoma and play an important role in hepatocarcinogenesis.
E2F-4hepatocellular carcinomamicrosatellite instabilityTGF-β type II receptor
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