1. Droplet digital PCR detects high rate of TP53 R249S mutants in cell-free DNA of middle African patients with hepatocellular carcinoma.
- Author
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Marchio A, Amougou Atsama M, Béré A, Komas NP, Noah Noah D, Atangana PJA, Camengo-Police SM, Njouom R, Bekondi C, and Pineau P
- Subjects
- Adolescent, Adult, Aflatoxin B1 toxicity, Aged, Aged, 80 and over, Cameroon, Carcinoma, Hepatocellular chemically induced, Carcinoma, Hepatocellular genetics, Carcinoma, Hepatocellular virology, Case-Control Studies, Cell-Free Nucleic Acids blood, Central African Republic, DNA, Viral genetics, Female, Gene Expression, Hepatitis B Surface Antigens blood, Hepatitis B Surface Antigens genetics, Hepatitis B virus genetics, Hepatitis B virus isolation & purification, Hepatitis B, Chronic genetics, Hepatitis B, Chronic pathology, Hepatitis B, Chronic virology, Humans, Liver Neoplasms chemically induced, Liver Neoplasms genetics, Liver Neoplasms virology, Male, Middle Aged, Mutation Rate, Tumor Suppressor Protein p53 blood, Viral Load, alpha-Fetoproteins genetics, alpha-Fetoproteins metabolism, Carcinoma, Hepatocellular diagnosis, Cell-Free Nucleic Acids genetics, Hepatitis B, Chronic diagnosis, Liver Neoplasms diagnosis, Polymerase Chain Reaction methods, Tumor Suppressor Protein p53 genetics
- Abstract
Hepatocellular carcinoma (HCC) is still a major killing malignancy in sub-Saharan Africa. Lifelong intoxication with aflatoxin B1 is considered as one of the primary causes of this situation. The role of aflatoxin in HCC from a given population is commonly estimated through the prevalence of R249S mutation of TP53, a hallmark for previous exposure to the mycotoxin. However, the role of AFB1 is barely known in large part of Africa. We conducted a survey on circulating cell-free DNA from 149 patients with HCC and 213 control subjects with and without liver diseases from Cameroon and Central African Republic using droplet digital PCR technique. We observed a mutation prevalence of 24.8% (n = 37/149) in patients with tumor and 5.6% (n = 12/213) in controls (P = 2.2E-07). Patients with mutations usually displayed significantly increased circulating alpha-fetoprotein (AFP) values, high hepatitis B virus (HBV) DNA loads as well as worsened values of blood cells count. Interestingly, the fraction of droplets positive for R249S was significantly larger in patients with liver cancer (15.3 ± 3.7%) than in controls (0.5 ± 0.3%, P = 7.1E-04). Our survey indicates that AFB1 is instrumental for HCC development in Middle Africa and that droplet digital PCR might be used in the region both to diagnose HCC and to conduct public health surveys on populations at risk of chronic aflatoxin intoxication.
- Published
- 2018
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