Ser-249 p53 mutations in plasma DNA of patients with hepatocellular carcinoma from the Gambia

Background: A selective mutation, an arginine-to-serine substitution in cod on 249, of the p53 gene has been identified as a "hotspot" mutation in hepa tocellular carcinoma (HCC), This mutation occurs in populations that are ex posed to aflatoxins and have a high prevalence of hepatitis B virus carrier s. We evaluated whether this mutation could be detected in cell-free DNA is olated from the plasma of subjects from The Gambia to detect this mutation that is strongly associated with HCC. Methods: Fifty-three patients with HC C, 13 patients with cirrhosis, and 53 control subjects were prospectively r ecruited from The Gambia, Sixty patients, of non-African origin, with vario us liver pathologies were also selected from France. DNA was extracted and purified from 200-mu L aliquots of plasma. The Ser-249 p53 mutation was det ected by restriction endonuclease digestion of polymerase chain reaction pr oducts from exon 7 and was confirmed by direct sequencing of the amplified DNA, Results: The Ser-249 p53 mutation was detected in plasma DNA from 19 ( 36%) of the 53 patients with HCC, two (15%) of the 13 patients with cirrhos is, and three (6%) of the 53 control subjects. This mutation was not detect ed in any plasma DNA from the European patients. The adjusted odds ratio fo r having the mutation was 16.4 (95% confidence interval = 3.0-90.5) for pat ients with HCC compared with the control subjects. Conclusion: The Ser-249 p53 mutation in plasma DNA is strongly associated with HCC in Gambian patie nts, This mutation was also detected at a much lower prevalence in plasma D NA from Gambian patients with cirrhosis and in Gambian control subjects, fi ndings that may lead to the earlier detection of HCC. Use of the Ser-249 p5 3 mutation should facilitate further molecular epidemiologic studies on the development of HCC.