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Evaluation of INK4A promoter methylation using pyrosequencing and circulating cell-free DNA from patients with hepatocellular carcinoma.
Huang, Gengming; Krocker, Joseph D; Kirk, Jason L; Merwat, Shehzad N; Ju, Hyunsu; Soloway, Roger D; Wieck, Lucas R; Li, Albert; Okorodudu, Anthony O; Petersen, John R; Abdulla, Nihal E; Duchini, Andrea; Cicalese, Luca; Rastellini, Cristiana; Hu, Peter C; Dong, Jianli.
Afiliación
  • Huang G; Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA.
  • Krocker JD; Molecular Genetic Technology Program, School of Health Sciences, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
  • Kirk JL; Medicine, University of Texas Medical Branch, Galveston, TX, USA.
  • Merwat SN; Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA.
  • Ju H; Preventive Medicine and Community Health, University of Texas Medical Branch, Galveston, TX, USA.
  • Soloway RD; Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA.
  • Wieck LR; Medicine, University of Texas Medical Branch, Galveston, TX, USA.
  • Li A; Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA.
  • Okorodudu AO; Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA.
  • Petersen JR; Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA.
  • Abdulla NE; Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA.
  • Duchini A; Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA.
  • Cicalese L; Surgery, University of Texas Medical Branch, Galveston, TX, USA.
  • Rastellini C; Surgery, University of Texas Medical Branch, Galveston, TX, USA.
  • Hu PC; Molecular Genetic Technology Program, School of Health Sciences, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
  • Dong J; Department of Pathology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-0743, USA.
Clin Chem Lab Med ; 52(6): 899-909, 2014 Jun.
Article en En | MEDLINE | ID: mdl-24406287
BACKGROUND: Hyper-methylation of CpG dinucleotides in the promoter region of inhibitor of cyclin-dependent kinase 4A (INK4A) has been reported in 60%-80% of hepatocellular carcinoma (HCC). As INK4A promoter hypermethylation event occurs early in HCC progression, the quantification of INK4A promoter methylation in blood sample may represent a useful biomarker for non-invasive diagnosis and prediction of response to therapy. METHODS: We examined INK4A promoter methylation using circulating cell-free DNA (ccfDNA) in a total of 109 serum specimens, including 66 HCC and 43 benign chronic liver diseases. Methylation of the individual seven CpG sites was examined using pyrosequencing. RESULTS: Our results showed that there were significantly higher levels of methylated INK4A in HCC specimens than controls and that the seven CpG sites had different levels of methylation and might exist in different PCR amplicons. The area under receiver operating characteristic (ROC) curve was 0.82, with 65.3% sensitivity and 87.2% specificity at 5% (LOD), 39.0% sensitivity and 96.5% specificity at 7% LOD, and 20.3% sensitivity and 98.8% specificity at 10% LOD, respectively. CONCLUSIONS: Our results support additional studies incorporating INK4A methylation testing of ccfDNA to further validate the diagnostic, predictive, and prognostic characteristics of this biomarker in HCC patients. The knowledge of the existence of epi-alleles should help improve assay design to maximize detection.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: ADN / Regiones Promotoras Genéticas / Análisis de Secuencia de ADN / Carcinoma Hepatocelular / Metilación de ADN / Inhibidor p16 de la Quinasa Dependiente de Ciclina / Neoplasias Hepáticas Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Clin Chem Lab Med Asunto de la revista: QUIMICA CLINICA / TECNICAS E PROCEDIMENTOS DE LABORATORIO Año: 2014 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Alemania
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: ADN / Regiones Promotoras Genéticas / Análisis de Secuencia de ADN / Carcinoma Hepatocelular / Metilación de ADN / Inhibidor p16 de la Quinasa Dependiente de Ciclina / Neoplasias Hepáticas Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Clin Chem Lab Med Asunto de la revista: QUIMICA CLINICA / TECNICAS E PROCEDIMENTOS DE LABORATORIO Año: 2014 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Alemania