A comprehensive summary of the data from our laboratory and the literature, based on a large number (>1000) of individual cases of hepatocellular carcinoma, is presented here and shows the following: 1) A high level and high prevalence of exposure to aflatoxins occur in West Africa, Mozambique, and some regions of China; 2) a high prevalence of the 249ser p53 mutation is detected in these countries; and 3) hepatocellular carcinomas from countries with low or no exposure to aflatoxins show a very low prevalence of the 249ser p53 mutation and distinctly different p53 mutation spectra, probably indicating different etiologies.
A G to T mutation has been observed at the third position of codon 249 of the p53 tumor-suppressor gene in over 50% of the hepatocellular carcinoma cases associated with high exposure to aflatoxin B(1) (AFB(1)).
A large fraction of the p53 mutations in lung cancers are G-->T transversions, a type of mutation that is infrequent in other tumors aside from hepatocellular carcinoma.
A mutation in codon 249 of the TP53 gene (249(Ser)), related to aflatoxin B(1) exposure, has previously been associated with hepatocellular carcinoma risk.
A mutation in the tumor suppressor p53 gene resulting in an Arg-->Ser substitution in position 249 is found frequently in human hepatocellular carcinomas associated with hepatitis B infection and with aflatoxin exposure.
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.
A number of recently published NGS studies on HCCs have not only confirmed previously known mutations in CTNNB1 and TP53 in HCC, but also identified novel genetic alterations in HCC including mutations in genes involved in epigenetic regulation.
A patient with huge hepatocellular carcinoma who had a complete clinical response to p53 gene combined with chemotherapy and transcatheter arterial chemoembolization.
A selective mutation in TP53 (AGG-->AGT at codon 249, Arg-->Ser) has been identified as a hotspot in HCCs from such areas, reflecting DNA damage caused by aflatoxin metabolites.
A series of nine CC, 15 HCC-CC and three separated HCC and CC lesions ('collision tumors') were screened for loss of heterozygosity (LOH) using 400 microsatellite markers and for p53 and beta-catenin mutations.
A single base substitution at the third nucleotide of codon 249 of TP53 (R249S) is common in HCC in these regions and has been associated with aflatoxin-DNA adducts.
A specific missense mutation resulting from a guanine to thymine transversion at the third position of codon 249 in the p53 tumor suppressor gene has been reported in 10-70% of HCCs from areas of high dietary exposure to aflatoxin B1.
A specific missense mutation resulting from a guanine to thymine transversion at the third position of codon 249 in the p53 tumor suppressor gene has been reported in 10-70% of HCCs from areas of high dietary exposure to aflatoxin B(1.)
Aberrant p53 expression and cyclin D1 and E overexpression were observed exclusively in HCC lesions. pRb was positive in 85.6% of the HCC cases and was not related to any clinicopathological parameters.
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.
Activation of the insulin-like growth factor II transcription by aflatoxin B1 induced p53 mutant 249 is caused by activation of transcription complexes; implications for a gain-of-function during the formation of hepatocellular carcinoma.
Additionally, as overexpression of p53 mutants is frequently found in undifferentiated hepatocellular carcinomas, the same mechanisms may contribute to the lack of liver-specific gene transcription in these tumors.
Adenovirus-mediated p53 gene transfer can promote G(1)-phase arrest and cell apoptosis, thus sensitizing hepatocellular carcinoma cells to heavy-ion irradiation.