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. 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.
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. 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.
Authors: Jingjing Jiao; Weibo Niu; Ying Wang; Keith Baggerly; Yuanqing Ye; Xifeng Wu; Dewitt Davenport; Jose Luis Almeda; Monica M Betancourt-Garcia; R Armour Forse; Heather L Stevenson; Gordon P Watt; Joseph B McCormick; Susan P Fisher-Hoch; Laura Beretta Journal: Cancer Prev Res (Phila) Date: 2017-10-31
Authors: Kyle L Brown; Markus W Voehler; Shane M Magee; Constance M Harris; Thomas M Harris; Michael P Stone Journal: J Am Chem Soc Date: 2009-11-11 Impact factor: 15.419
Authors: Jeronimo A Nogueira; Suzane K Ono-Nita; Marcelo E Nita; Marcelo M T de Souza; Eliane P do Carmo; Evandro S Mello; Cristovan Scapulatempo; Denise C Paranaguá-Vezozzo; Flair J Carrilho; Venancio A F Alves Journal: BMC Cancer Date: 2009-06-26 Impact factor: 4.430