title: Detection of p53 Mutations in Circulating DNA of Transplanted Hepatocellular Carcinoma Patients as a Biomarker of Tumor Recurrence.
abstract: p53 is the most commonly mutated gene in malignant human cancers. To detect p53 mutations in circulating DNA (cirDNA) of transplanted hepatocellular carcinoma (HCC) patients could be an interesting approach to know of any tumor recurrence. In this study, our objective was to determine the utility of this method in the diagnosis and the prognosis of HCC tumor recurrence.Twenty four liver transplanted HCC patients were included in the study together with a group of healthy controls. Detection of the specific p53 mutation in cirDNA was performed by high-resolution melting PCR (HRM-PCR) and COLD-PCR immediately before the transplantation. Serum anti-p53 was also determined using a p53-autoantibody ELISA kit.The results of the HRM-PCR and COLD-PCR showed two well-differentiated groups of transplanted patients after normalization by healthy controls. These data allow us to distinguish between patients with p53 mutated cirDNA and those with wild type cirDNA. Moreover, we have found that most of p53 mutated patients also presented elevated anti-p53 antibodies. The present results indicate that it is possible to detect mutated p53 genes with the cirDNA and that this could be used as a biomarker of tumor recurrence during the clinical evolution of the transplanted patients.
authors.affiliation: Department of Clinical Biochemistry, Instituto de Biomedicina de Sevilla (IBiS/Csic/SAS/University of Seville), University Hospital Virgen del Rocío of Seville, Seville, Spain.
authors.forename: N
authors.initials: N
authors.lastname: García-Fernández
authors.affiliation: Department of Clinical Biochemistry, Instituto de Biomedicina de Sevilla (IBiS/Csic/SAS/University of Seville), University Hospital Virgen del Rocío of Seville, Seville, Spain.
authors.forename: Hada C
authors.initials: HC
authors.lastname: Macher
authors.affiliation: Department of Clinical Biochemistry, Instituto de Biomedicina de Sevilla (IBiS/Csic/SAS/University of Seville), University Hospital Virgen del Rocío of Seville, Seville, Spain.
authors.forename: Amalia
authors.initials: A
authors.lastname: Rubio
authors.affiliation: Department of Clinical Biochemistry, Instituto de Biomedicina de Sevilla (IBiS/Csic/SAS/University of Seville), University Hospital Virgen del Rocío of Seville, Seville, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Jiménez-Arriscado
authors.affiliation: Hepatobiliary and Liver Transplantation Unit, Virgen del Rocío University Hospital, Seville, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Bernal-Bellido
authors.affiliation: Department of Clinical Biochemistry, Instituto de Biomedicina de Sevilla (IBiS/Csic/SAS/University of Seville), University Hospital Virgen del Rocío of Seville, Seville, Spain.
authors.forename: M L
authors.initials: ML
authors.lastname: Bellido-Díaz
authors.affiliation: Hepatobiliary and Liver Transplantation Unit, Virgen del Rocío University Hospital, Seville, Spain.
authors.forename: G
authors.initials: G
authors.lastname: Suárez-Artacho
authors.affiliation: Department of Clinical Biochemistry, Instituto de Biomedicina de Sevilla (IBiS/Csic/SAS/University of Seville), University Hospital Virgen del Rocío of Seville, Seville, Spain.
authors.forename: Juan M
authors.initials: JM
authors.lastname: Guerrero
authors.affiliation: Hepatobiliary and Liver Transplantation Unit, Virgen del Rocío University Hospital, Seville, Spain.
authors.forename: M A
authors.initials: MA
authors.lastname: Gómez-Bravo
authors.affiliation: Department of Clinical Biochemistry, Instituto de Biomedicina de Sevilla (IBiS/Csic/SAS/University of Seville), University Hospital Virgen del Rocío of Seville, Seville, Spain. molinero@us.es.
authors.forename: Patrocinio
authors.initials: P
authors.lastname: Molinero
mesh_terms: D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D016031:Liver Transplantation; D009154:Mutation; D009364:Neoplasm Recurrence, Local; D016133:Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000276:immunology
chemical_list: D001323:Autoantibodies; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D016159:Tumor Suppressor Protein p53
keywords: Anti-p53 antibodies; Circulating DNA; Hepatocellular carcinoma; p53 mutation