Tumour suppressor p53 and Rb genes in human hepatocellular carcinoma.
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.
Lin
Y
Y
Department of Microbiology, National University of Singapore, Singapore.
Shi
C Y
CY
Li
B
B
Soo
B H
BH
Mohammed-Ali
S
S
Wee
A
A
Oon
C J
CJ
Mack
P O
PO
Chan
S H
SH
D000818:Animals; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000821:virology; D002415:Cats; D004247:DNA / Q000032:analysis; D016161:Genes, Retinoblastoma / Q000235:genetics / Q000502:physiology; D016147:Genes, Tumor Suppressor / Q000235:genetics / Q000502:physiology; D016158:Genes, p53 / Q000235:genetics / Q000502:physiology; D006509:Hepatitis B / Q000150:complications; D006515:Hepatitis B virus / Q000302:isolation & purification; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000821:virology; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D014407:Tumor Cells, Cultured
D004247:DNA