Absence of mutation of the p73 gene localized at chromosome 1p36.3 in hepatocellular carcinoma.
Accumulating evidence has demonstrated that aberration of the p53 tumour-suppressor gene is one of the pivotal genetic events in hepatocellular carcinogenesis. Recent reports suggest that the product of hepatitis B virus (HBV) interacts with p53 and that the hepatitis C virus (HCV) core protein reduces p53 expression. A novel p73 gene, which is related to p53, has recently been identified and mapped to chromosome 1p36.3, which is a locus of multiple tumour-suppressor genes for many cancers, including hepatocellular carcinoma (HCC) and neuroblastoma. Here, we investigated mRNA expression, allelotype and mutation of p73 in 48 HCCs obtained from untreated patients. Reverse transcriptase polymerase chain reaction (RT-PCR) revealed that p73 mRNA was expressed ubiquitously at low levels in all the tumour tissues, as well as in the adjacent normal liver tissues. The frequency of p73 loss of heterozygosity was observed in 20% of HCCs, but PCR-single strand conformation polymorphism (SSCP) analysis showed no mutations in the 48 tumours except for three types of polymorphisms. These results suggest that p73 may play a role in hepatocellular carcinogenesis in a different manner from a Knudson two-hit model. The regulatory mechanism of interaction between p73 and hepatitis viruses remains to be determined.
Mihara
M
M
Division of Biochemistry, Chiba Cancer Center Research Institute, Japan.
Nimura
Y
Y
Ichimiya
S
S
Sakiyama
S
S
Kajikawa
S
S
Adachi
W
W
Amano
J
J
Nakagawara
A
A
D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D002878:Chromosomes, Human, Pair 1; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics*; D016147:Genes, Tumor Suppressor; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D019656:Loss of Heterozygosity; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins
D017931:DNA Primers; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins