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

Gregory D. Kirk, Anne Marie Camus-Randon, Maimuna Mendy, James J. Goedert, Philippe Merle, Christian Trépo, Christian Bréchot, Pierre Hainaut, Ruggero Montesano

Research output: Contribution to journalArticlepeer-review

131 Scopus citations


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-μL 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)148-153
Number of pages6
JournalJournal of the National Cancer Institute
Issue number2
StatePublished - Jan 19 2000
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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