Other than site-specific aflatoxin B(1)-induced mutations, p53 coding region mutations are not frequently observed in most human primary hepatocellular carcinomas.
Hepatocellular carcinoma (HCC) is one of the most frequent-occurring malignant tumours worldwide, but molecular changes of tumour DNA, with the exception of viral integrations and p53 mutations, are poorly understood.
The relation between aflatoxin B1 (AFB1 )-related hepatocellular carcinomas (HCCs) and hot spot at codon 249 of the p53 gene has received a great deal of attention, but its significance is still controversial.
AGG to AGT transversion in codon 249 of exon 7 of the p53 gene occurs in over 50% of HCC from endemic regions, where both chronic infection with the hepatitis B virus (HBV) and exposure to carcinogens such as aflatoxin B1 (AFB1) prevail.
Inactivation of the p53 tumor suppressor gene by mutations and allelic deletions in about 30% of HCC cases has been associated predominantly with exposure to aflatoxin B1 and HBV infection.
The Ser-249 p53 mutation was detected in plasma DNA from 19 (36%) of the 53 patients with HCC, two (15%) of the 13 patients with cirrhosis, and three (6%) of the 53 control subjects.
ASPM overexpression is a molecular marker predicting enhanced invasive/metastatic potential of HCC, higher risk of ETR regardless of p53 mutation status and tumor stage, and hence poor prognosis.
The three factors (ALDOB down-regulation, HKII overexpression and p53 mutation) not only correlated with tumor progression, but also interacted with one another, leading to a more aggressive HCC with a portal vein invasion and various extent of intrahepatic metastasis by more than four-fold (ps<1x10(-6)) and frequent ETR by more than two-fold (ps<0.0001) compared with HCCs without the events.
The most frequent mutation in HCC in populations exposed to a high dietary intake of aflatoxin B1 (AFB1) is an AGGarg-->AGTser missense mutation in codon 249 of the p53 gene.
Thus, in this investigation, the p53 and XRCC1 gene polymorphisms using the standard protocols were also assessed to find out whether these genes may be associated with HCC susceptibility.
Our results suggest that gain of chromosome 17 and deletion of the p53 locus could represent early genetic events, prior to overexpression of p53 protein due to mutation, in early stage HCC.
Moreover, these M6P/IGF2R 3'UTR mutations and the TP53 mutations detected previously were mutually exclusive in most of the tumors, suggesting two independent pathways to HCC development, with the TP53 pathway being more favored with increasing radiation dose than the M6P/IGF2R pathway.
Here we report a unique mechanism underlying the GOF of p53-R249S (p53-RS), a p53 mutant frequently detected in human hepatocellular carcinoma (HCC) that is highly related to hepatitis B infection and aflatoxin B1.
We concluded that p53mt249 stimulates IGF-II dependent IGF-IR signaling by upregulating the expression of both ligand (IGF-II) and receptor (IGF-IR) through an autocrine and/or paracrine loop and we outline the physiological significance of potentiation of IGF-IR by p53 mutation in the development of hepatocellular carcinoma (HCC).
Mutated p53 acts as a dominant oncogene and alterations in the p53 gene are described in a large number of patients with hepatocellular carcinoma (HCC).
Our aim was to analyze the spectrum of p53 mutations in tumor tissues from subjects with HCC in Egypt, where there is a rising incidence of HCC due to hepatitis C virus (HCV).
CD44 rs187115 might be involved in CD44 isoform expression of p53 stress response in HCC and provide a marker for predicting worst-case prognosis of HCC.