title: Ser-249TP53 mutation in tumour and plasma DNA of hepatocellular carcinoma patients from a high incidence area in the Gambia, West Africa.
abstract: Hepatocellular carcinoma (HCC) is frequent in areas of high exposure to aflatoxin and high prevalence of HBV infection, such as western Africa and south-east China. A selective mutation in TP53 (AGG-->AGT at codon 249, Arg-->Ser) has been identified as a hotspot in HCCs from such areas, reflecting DNA damage caused by aflatoxin metabolites. Recent studies have shown that circulating free DNA can be retrieved from human plasma, and it is hypothesised that plasma DNA may serve as a source for biomarkers of tumorigenic processes. In our study, we have determined the prevalence of Ser-249 mutation, using a PCR-restriction digestion method, with selective use of short oligonucleotide mass spectrometry analysis (SOMA), in a series of 29 biopsy specimens of HCC from The Gambia in West Africa. Overall, we identified the Ser-249 mutation in 35% (10/29) of the tumours. In parallel, we tested 17 plasma samples from HCC patients with matching tumour tissue. The 249 status concordance between tumour tissues and matched plasma was 88.5%. These results indicate that the Ser-249 mutation is common in HCC in The Gambia (35%), although a higher prevalence has been reported in other regions with high population exposure to aflatoxin (e.g., eastern China: >50%). Moreover, our studies indicate that plasma is a convenient source of liver tumour-derived DNA, thus holding promise for earlier detection and diagnosis of cancer.
authors.affiliation: International Agency for Research on Cancer and Gambia Hepatitis Intervention Study, Lyon, France.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Szymańska
authors.forename: Olufunmilayo A
authors.initials: OA
authors.lastname: Lesi
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Kirk
authors.forename: Omar
authors.initials: O
authors.lastname: Sam
authors.forename: Philippe
authors.initials: P
authors.lastname: Taniere
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Scoazec
authors.forename: Maimuna
authors.initials: M
authors.lastname: Mendy
authors.forename: Marlin D
authors.initials: MD
authors.lastname: Friesen
authors.forename: Hilton
authors.initials: H
authors.lastname: Whittle
authors.forename: Ruggero
authors.initials: R
authors.lastname: Montesano
authors.forename: Pierre
authors.initials: P
authors.lastname: Hainaut
mesh_terms: D000328:Adult; D000348:Aflatoxins / Q000494:pharmacology; D000368:Aged; D000369:Aged, 80 and over; D000956:Antigens, Viral / Q000737:chemistry; D001706:Biopsy; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D004247:DNA / Q000235:genetics*; D004249:DNA Damage; D004262:DNA Restriction Enzymes / Q000494:pharmacology; D005091:Exons; D005260:Female; D005714:Gambia; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000235:genetics*; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D012694:Serine / Q000737:chemistry*; D016159:Tumor Suppressor Protein p53 / Q000097:blood* / Q000235:genetics*
chemical_list: D000348:Aflatoxins; D000956:Antigens, Viral; D016159:Tumor Suppressor Protein p53; D012694:Serine; D004247:DNA; D004262:DNA Restriction Enzymes