p73 is up-regulated in a subset of hepatocellular carcinomas

Loss of heterozygosity (LOH) at 1p36 occurs in a number of solid tumors inc luding hepatocellular carcinoma (HCC). Recently, a novel gene, p73, has bee n identified at 1p36.33. p73 is structurally and functionally related to p5 3 located at 17p13.1, which is a target for inactivation in HCCs. p73 produ ces at least two splicing variants, p73 alpha and beta, and a polymorphism in exon 2 results in two alleles, GC or AT. Initially, only the AT allele a nd p73 alpha transcripts were identified in malignant cell lines, suggestin g a role for these in the malignant phenotype. The aims of this study were to determine the extent of LOH at 1p36 and 17p13.1 in HCCs from Australia a nd South Africa, and to identify patterns of P73 mRNA and p73 and p53 prote in expression. LOH at 1p36 was found in 8 of 25 Australian and 6 of 10 Sout h African cases. p73 mRNA expression occurred in 8 HCCs, but not in nonmali gnant liver tissue. Two of these 8 HCCs had LOH of 1p36. Both alpha and bet a transcripts were observed in GC/GC homozygotes and GC/AT heterozygotes. N o p73 protein expression was observed by immunohistochemistry in nonmaligna nt liver tissue or in HCC. p53 inactivation appeared to be associated with up-regulation of p73 expression, suggesting a compensatory role for p73 in this situation. The LOH at 1p36 implies a liver-specific tumor suppressor g ene is in this region. However, the upregulation of p73 mRNA suggests p73 i s not the target of this loss.