TP53 and CTNNB1 are the next most prevalent mutations, affecting 25%-30% of HCC patients, that, in addition to low-frequency mutated genes (eg, AXIN1, ARID2, ARID1A, TSC1/TSC2, RPS6KA3, KEAP1, MLL2), help define some of the core deregulated pathways in HCC.
Using short hairpin RNA against p53, transient ectopic expression of wild-type p53 or mutant p53 (R248W or R175H), and a p53- and p21-dependent luciferase reporter assay, we demonstrated that growth arrest and apoptosis of FaDu (human pharyngeal squamous cell carcinoma), Hep3B (hepatoma), and MG-63 (osteosarcoma) cells induced by aloe-emodin (AE) are p53-independent.
Although its metabolites bind at several positions in TP53, a mutation at codon 249 (AGG to AGT, arginine to serine, p.R249S) accounts for 90% of TP53 mutations in AFB(1)-related HCC.
This study provides direct evidence that telomerase is a critical component for in vivo progression of p53 mutant HCC with short telomeres in the chronically damaged liver.
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.
It was also found that the most common p53 mutation in hepatocellular carcinomas (R249S) was a much better indicator for poor prognosis than TP53 mutations as a whole.
All tumours had the wild-type sequence at codon 249, which has been reported to be a mutational hot spot in the p53 gene in HCCs from high incidence areas, such as China and Southern Africa.
Human hepatocellular carcinomas (HCCs) are often found to have mutant p53, or sometimes may have dysfunctional p53 as a result of its being bound by viral or cellular proteins.
The prevalence of the p53 codon 249 mutation was expressed as a percentage amplifiable DNA samples analyzed from HCC patients while that of controls was expressed in the same way.
In this report, we show that the synergistic action of HBx and p53 mutation triggers progressive hepatocellular carcinoma (HCC) formation via src activation in zebrafish.
DNA analysis revealed allele loss on chromosome 17 (17p13, near the locus of p53 tumour suppressor gene) in the hepatocellular carcinoma but not in the adenoma.
Recently, it has been reported that exposure of the wild-type p53 human lymphoblastoid cell line to 4-HNE causes a high frequency of G to T transversion mutations at the third base of codon 249 (-AGG*-) in the p53 gene, a mutational hotspot in human cancers, particularly hepatocellular carcinoma.