Hepatocellular carcinoma (HCC) is frequent in areas of high exposure to afatoxin and high prevalence of Hepatitis B virus infection, such as western Africa and south-east China. A selective mutation in TP53 (AGG-->AGT at codon 249, Arg-->Ser) has been identifed as a hotspot in HCCs from such areas, reflecting DNA damage caused by afatoxin metabolites. Recent studies have shown that circulating free DNA can be retrieved from human plasma, and it is hypothesised that plasma DNA may serve as a source for biomarkers of tumorigenic processes.

Short Oligonucleotide Mass Analysis (SOMA) is a technique in which short fragments of DNA, generated by PCR amplification and restriction digestion, are analysed by Electrospray Mass Spectrometry. Using an internal standard plasmid containing a modified portion of the TP53 gene, the SOMA method has been modified to quantitatively measure levels of this mutation in free-circulating DNA in human plasma. The approach has been applied to measure the prevalence of Ser-249 TP53 mutation in the plasma of HCC case and control subjects from The Gambia in West Africa.

Our studies indicate that measurement of such mutations in plasma DNA holds promise for earlier detection and diagnosis of cancer.