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Abstract
Hepatocellular Carcinoma (HCC) in high-incidence areas (sub-Saharan Africa, South-Eastern
Asia) often contains a somatic mutation at codon 249 in TP53 (R249S). This mutation
is rare in low-incidence areas of Europe and the United States. There is evidence
that R249S occurs as the result of mutagenesis by aflatoxin in a context of HBV chronic
infection. Here, we summarize the mechanisms of R249S formation and the possible role
of p.R249S protein in HCC pathogenesis. Next, we discuss the significance of R249S
as a biomarker to study the natural history of HCC and as a target for therapeutic
approaches aimed at restoring wild-type p53 activity.