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|Title:||Tumour suppressor p53 and Rb genes in human hepatocellular carcinoma|
Hepatitis B vrius
Restriction fragment length polymorphism
|Citation:||Lin, Y., Shi, C.Y., Li, B., Soo, B.H., Mohammed-Ali, S., Wee, A., Oon, C.J., Mack, P.O.P., Chan, S.H. (1996-01). Tumour suppressor p53 and Rb genes in human hepatocellular carcinoma. Annals of the Academy of Medicine Singapore 25 (1) : 22-30. ScholarBank@NUS Repository.|
|Abstract:||Aberrations of the p53 and Rb tumour suppressor genes were examined in 12 human hepatocellular carcinoma (HCC)-derived cell lines from different geographic areas and 9 local HCCs by restriction fragment length polymorphisms (RFLP), polymerase chain reaction-single-strand conformation polymorphisms (PCR-SSCP) and DNA sequencing. The relationships between genetic changes and hepatitis B virus (HBV) DNA integration in samples were compared. None of the cell lines and tumours showed structural changes in the Rb gene, while 6 cell lines and 2 tumours had mutation or deletion in exons 5 to 8 of p53. Mutations include an AGG→AGT (Arg→Ser) transversion at codon 249 in PLC/PRF/5 and Mahlavu, an AAT→AAA (Asn→Cys) transversion at codon 200 in TONG/HCC, an AAG→GAG (Lys→Glu) transition at codon 139 in HCC-T, a CAT→CGT (His→Arg) transition at codon 214 in SC4, and a CCC→CTC (Pro→Leu) transition at codon 250 in SC8. In Huh4, an 18-bp deletion from codon 264 to 270 resulted in loss of Leu-Gly-Arg-Asn-Ser-Phe from the amino acid sequences 265 to 270, whereas Hep3B had a 7-kb deletion after exon 7 of p53. Our data indicate that whereas Rb may not have pleiotropic effects on HCC, p53 aberrations are frequently involved in hepatocarcinogenesis. Further, HBV infection appears to be unrelated to the micro-genetic changes of p53. The G to T codon-249-mutation is consistent with HCCs arising from areas at high risk for both aflatoxin B1 (AFB1) exposure and HBV infection.|
|Source Title:||Annals of the Academy of Medicine Singapore|
|Appears in Collections:||Staff Publications|
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