Hepatitis B virus integration event in human chromosome 17p near the p53 gene identifies the region of the chromosome commonly deleted in virus-positive hepatocellular carcinomas.
For example, an informative p53 mutational spectrum of frequent G----T transversions in codon 249 is found in hepatocellular carcinomas from either Qidong, People's Republic of China, or southern Africa.
Mutant p53 protein was detected in the nuclei of HCCs from 14 (61%) of 23 patients from China and from three (30%) of 10 patients and six (60%) of 10 patients, respectively, from the two regions of the United States.
These findings show that p53 mutations are infrequently involved in the malignant transformation of hepatocytes in an area of low hepatocellular carcinoma prevalence.
By the PCR-SSCP analysis of DNAs from surgical specimens of human cancers, mutated ras genes (17%) and aberrations of tumor suppressor p53 gene (53%) including loss of one of the two alleles and a mutation in the remaining allele were detected in lung carcinomas and aberrations of both of the p53 and retinoblastoma (RB) genes were detected exclusively in advanced hepatocellular carcinomas.
We have examined 13 cases of human hepatocellular carcinomas from Germany for the presence of p53 aberrations in exons 4 to 8 of the gene by single-strand conformation polymorphism and restriction fragment-length polymorphism analyses and by sequencing of polymerase chain reaction products.
Abnormalities of the p53 gene have been identified in many malignancies, with reports of aberration in over half of colorectal, lung, breast and hepatocellular carcinoma cases.
A mutational "hotspot" in the p53 gene in human hepatocellular carcinomas has been identified that could reflect exposure to a specific carcinogen, one candidate being aflatoxin B1.
Therefore, p53 gene mutation is suggested to occur independently of the type of viral infection or status of preexisting liver disease and to occur preferentially in moderately and poorly differentiated HCCs in association with or after loss of another p53 allele as a late event of HCC progression.
Immunostaining with monoclonal pAb 1801 revealed expression of p53 protein in tumor-cell nuclei in one HCV-associated HCC, and in no case of HBV-associated HCC, while the nuclei of adjacent hepatocytes were negative.