Genetic alternations of p73 are infrequent but may occur in early stage hepatocellular carcinoma.
p73, a structural homologue of the tumor suppressor gene, p53, has recently been identified and mapped to chromosome 1p36, where genomic loss of heterozygosity (LOH) often occurs in human hepatocellular carcinoma (HCC). To determine whether p73 is involved in the development of HCC and whether there is an inverse correlation between the mutations of p73 and p53, we examined 22 paired tumors/noncancerous liver tissues for allelic expression, LOH and mutation of p73 and for mutation of p53. p73 was biallelically expressed in noncancerous liver tissues and in 7 out of the 8 informative tumors. One tumor tissue expressed only a single allele. LOH of p73 was found in 2 out of the 11 (18%) informative cases. A tumor-specific five-nucleotide deletion mutation causing a reading frameshift/early truncation of p73 DNA-binding domain was found, in which case no concomitant mutation in the DNA-binding domain of p53 was identified. Nine out of the 22 cases (41%) contained tumor-specific mutations in the DNA-binding domain of p53. Two of the three cases with p73 genetic alternations had a tumor size of less than 2 centimeters. These results suggest that p73 is a biallelically expressed gene in the liver and that allelic loss and mutation of p73 is infrequent and may occur early in HCC. p73 is unlikely to be the putative tumor suppressor gene located at chromosome 1p36 in HCC.
Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung University, Taipei, Taiwan.
C Y
CY
Peng
S L
SL
Tsai
C T
CT
Yeh
S P
SP
Hung
M F
MF
Chen
T C
TC
Chen
C M
CM
Chu
Y F
YF
Liaw
D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D016147:Genes, Tumor Suppressor; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics*; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D025521:Tumor Suppressor Proteins
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins