Specific p53 mutations detected in plasma and tumors of hepatocellular carcinoma patients by electrospray ionization mass spectrometry

Hepatocellular carcinoma (HCC), a common cause of cancer deaths worldwide, has several major etiological risk factors, including infection with the he patitis viruses and exposure to aflatoxin B-1. A specific missense mutation resulting from a guanine to thymine transversion at the third position of codon 249 in the p53 tumor suppressor gene has been reported in 10-70% of H CCs from areas of high dietary exposure to aflatoxin B-1. Short oligonucleo tide mass analysis was compared with DNA sequencing in 25 HCC samples for s pecific p53 mutations. Mutations were detected in 10 samples by short oligo nucleotide mass analysis in agreement with DNA sequencing. Analysis of anot her 20 plasma and tumor pairs showed 11 tumors containing the specific muta tion, and this change was detected in six of the paired plasma samples. Fou r of the plasma samples had detectable levels of the mutation; however, the tumors were negative, suggesting possible multiple independent HCCs. Ten p lasma samples from healthy individuals were all negative. This molecular di agnostic technique has implications for prevention trials and for the early diagnosis of HCC.