title: Ser-249 p53 mutations in plasma DNA of patients with hepatocellular carcinoma from The Gambia.
abstract: BACKGROUND
  A selective mutation, an arginine-to-serine substitution in codon 249, of the p53 gene has been identified as a "hotspot" mutation in hepatocellular carcinoma (HCC). This mutation occurs in populations that are exposed to aflatoxins and have a high prevalence of hepatitis B virus carriers. We evaluated whether this mutation could be detected in cell-free DNA isolated from the plasma of subjects from The Gambia to detect this mutation that is strongly associated with HCC.
  
  
  METHODS
  Fifty-three patients with HCC, 13 patients with cirrhosis, and 53 control subjects were prospectively recruited from The Gambia. Sixty patients, of non-African origin, with various liver pathologies were also selected from France. DNA was extracted and purified from 200-microL aliquots of plasma. The Ser-249 p53 mutation was detected by restriction endonuclease digestion of polymerase chain reaction products 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 cirrhosis, and three (6%) of the 53 control subjects. This mutation was not detected in any plasma DNA from the European patients. The adjusted odds ratio for having the mutation was 16.4 (95% confidence interval = 3.0-90.5) for patients with HCC compared with the control subjects.
  
  
  CONCLUSIONS
  The Ser-249 p53 mutation in plasma DNA is strongly associated with HCC in Gambian patients. This mutation was also detected at a much lower prevalence in plasma DNA from Gambian patients with cirrhosis and in Gambian control subjects, findings that may lead to the earlier detection of HCC. Use of the Ser-249 p53 mutation should facilitate further molecular epidemiologic studies on the development of HCC.
authors.affiliation: International Agency for Research on Cancer, Banjul, The Gambia.
authors.forename: G D
authors.initials: GD
authors.lastname: Kirk
authors.forename: A M
authors.initials: AM
authors.lastname: Camus-Randon
authors.forename: M
authors.initials: M
authors.lastname: Mendy
authors.forename: J J
authors.initials: JJ
authors.lastname: Goedert
authors.forename: P
authors.initials: P
authors.lastname: Merle
authors.forename: C
authors.initials: C
authors.lastname: Trépo
authors.forename: C
authors.initials: C
authors.lastname: Bréchot
authors.forename: P
authors.initials: P
authors.lastname: Hainaut
authors.forename: R
authors.initials: R
authors.lastname: Montesano
mesh_terms: D000328:Adult; D000348:Aflatoxins / Q000009:adverse effects; D000368:Aged; D000369:Aged, 80 and over; D001120:Arginine / Q000235:genetics; D044383:Black People / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000235:genetics*; D016022:Case-Control Studies; D004273:DNA, Neoplasm / Q000235:genetics; D004720:Endonucleases / Q000378:metabolism; D005260:Female; D005602:France; D005714:Gambia; D006509:Hepatitis B / Q000150:complications; D006801:Humans; D008103:Liver Cirrhosis / Q000235:genetics; D008113:Liver Neoplasms / Q000209:etiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology; D009154:Mutation; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D015995:Prevalence; D011446:Prospective Studies; D017422:Sequence Analysis, DNA / Q000379:methods; D012694:Serine / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: D000348:Aflatoxins; D004273:DNA, Neoplasm; D016159:Tumor Suppressor Protein p53; D012694:Serine; D001120:Arginine; D004720:Endonucleases