Quantitative Analysis of Plasma TP53 249Ser-Mutated DNA by Electrospray Ionization Mass Spectrometry

A mutation in codon 249 of the TP53 gene (249Ser), related to aflatoxin B1 exposure, has previously been associated with hepatocellular carcinoma risk. Using a novel internal stan-dard plasmid, plasma concentrations of 249Ser-mutated DNA were quantified by electrospray ionization mass spectrome-try in 89 hepatocellular carcinoma cases, 42 cirrhotic patients, and 131 nonliver diseased control subjects, all from highly aflatoxin-exposed regions of The Gambia. The hepatocellular carcinoma cases had higher median plasma concentrations of 249Ser (2,800 copies/mL; interquartile range: 500-11,000) compared with either cirrhotic (500 copies/mL; interquartile range: 500-2,600) or control subjects (500 copies/mL; inter-quartile range: 500-2,000; P < 0.05). About half (52%) of the hepatocellular carcinoma cases had>2,500 copies of 249Ser/m