Genome-Wide and Gene-Specific Epigenomic Platforms for Hepatocellular Carcinoma Biomarker Development Trials
The majority of the epigenomic reports in hepatocellular carcinoma have focused on identifying novel differentially methylated drivers or passengers of the oncogenic process. Few reports have considered the technologies in place for clinical translation of newly identified biomarkers. The aim of thi...
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| Format: | Article |
| Language: | English |
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Wiley
2014-01-01
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| Series: | Gastroenterology Research and Practice |
| Online Access: | http://dx.doi.org/10.1155/2014/597164 |
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| author | Christina Michailidi Ethan Soudry Mariana Brait Leonel Maldonado Andrew Jaffe Carmen Ili-Gangas Priscilla Brebi-Mieville Jimena Perez Myoung Sook Kim Xiaoli Zhong Quiang Yang Blanca Valle Stephen J. Meltzer Michael Torbenson Manel Esteller David Sidransky Rafael Guerrero-Preston |
| author_facet | Christina Michailidi Ethan Soudry Mariana Brait Leonel Maldonado Andrew Jaffe Carmen Ili-Gangas Priscilla Brebi-Mieville Jimena Perez Myoung Sook Kim Xiaoli Zhong Quiang Yang Blanca Valle Stephen J. Meltzer Michael Torbenson Manel Esteller David Sidransky Rafael Guerrero-Preston |
| author_sort | Christina Michailidi |
| collection | DOAJ |
| description | The majority of the epigenomic reports in hepatocellular carcinoma have focused on identifying novel differentially methylated drivers or passengers of the oncogenic process. Few reports have considered the technologies in place for clinical translation of newly identified biomarkers. The aim of this study was to identify epigenomic technologies that need only a small number of samples to discriminate HCC from non-HCC tissue, a basic requirement for biomarker development trials. To assess that potential, we used quantitative Methylation Specific PCR, oligonucleotide tiling arrays, and Methylation BeadChip assays. Concurrent global DNA hypomethylation, gene-specific hypermethylation, and chromatin alterations were observed as a hallmark of HCC. A global loss of promoter methylation was observed in HCC with the Illumina BeadChip assays and the Nimblegen oligonucleotide arrays. HCC samples had lower median methylation peak scores and a reduced number of significant promoter-wide methylated probes. Promoter hypermethylation of RASSF1A, SSBP2, and B4GALT1 quantified by qMSP had a sensitivity ranging from 38% to 52%, a specificity of 100%, and an AUC from 0.58 to 0.75. A panel combining these genes with HCC risk factors had a sensitivity of 87%, a specificity of 100%, and an AUC of 0.91. |
| format | Article |
| id | doaj-art-f434e96044c64860b064a11431f6c738 |
| institution | Kabale University |
| issn | 1687-6121 1687-630X |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Gastroenterology Research and Practice |
| spelling | doaj-art-f434e96044c64860b064a11431f6c7382025-02-03T05:58:16ZengWileyGastroenterology Research and Practice1687-61211687-630X2014-01-01201410.1155/2014/597164597164Genome-Wide and Gene-Specific Epigenomic Platforms for Hepatocellular Carcinoma Biomarker Development TrialsChristina Michailidi0Ethan Soudry1Mariana Brait2Leonel Maldonado3Andrew Jaffe4Carmen Ili-Gangas5Priscilla Brebi-Mieville6Jimena Perez7Myoung Sook Kim8Xiaoli Zhong9Quiang Yang10Blanca Valle11Stephen J. Meltzer12Michael Torbenson13Manel Esteller14David Sidransky15Rafael Guerrero-Preston16Department of Otolaryngology, Division of Head and Neck Cancer Research, School of Medicine, The Johns Hopkins University, Baltimore, MD 21231, USADepartment of Otolaryngology, Division of Head and Neck Cancer Research, School of Medicine, The Johns Hopkins University, Baltimore, MD 21231, USADepartment of Otolaryngology, Division of Head and Neck Cancer Research, School of Medicine, The Johns Hopkins University, Baltimore, MD 21231, USADepartment of Otolaryngology, Division of Head and Neck Cancer Research, School of Medicine, The Johns Hopkins University, Baltimore, MD 21231, USADepartment of Epidemiology, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, MD 21205, USADepartment of Otolaryngology, Division of Head and Neck Cancer Research, School of Medicine, The Johns Hopkins University, Baltimore, MD 21231, USADepartment of Otolaryngology, Division of Head and Neck Cancer Research, School of Medicine, The Johns Hopkins University, Baltimore, MD 21231, USADepartment of Otolaryngology, Division of Head and Neck Cancer Research, School of Medicine, The Johns Hopkins University, Baltimore, MD 21231, USADepartment of Otolaryngology, Division of Head and Neck Cancer Research, School of Medicine, The Johns Hopkins University, Baltimore, MD 21231, USADepartment of Otolaryngology, Division of Head and Neck Cancer Research, School of Medicine, The Johns Hopkins University, Baltimore, MD 21231, USADepartment of Otolaryngology, Division of Head and Neck Cancer Research, School of Medicine, The Johns Hopkins University, Baltimore, MD 21231, USADepartment of Otolaryngology, Division of Head and Neck Cancer Research, School of Medicine, The Johns Hopkins University, Baltimore, MD 21231, USADepartment of Gastroenterology, School of Medicine, The Johns Hopkins University, Baltimore, MD 21205, USADepartment of Pathology, School of Medicine, The Johns Hopkins University, Baltimore, MD 21205, USABellvitge Biomedical Research Institute, Barcelona, Catalonia, SpainDepartment of Otolaryngology, Division of Head and Neck Cancer Research, School of Medicine, The Johns Hopkins University, Baltimore, MD 21231, USADepartment of Otolaryngology, Division of Head and Neck Cancer Research, School of Medicine, The Johns Hopkins University, Baltimore, MD 21231, USAThe majority of the epigenomic reports in hepatocellular carcinoma have focused on identifying novel differentially methylated drivers or passengers of the oncogenic process. Few reports have considered the technologies in place for clinical translation of newly identified biomarkers. The aim of this study was to identify epigenomic technologies that need only a small number of samples to discriminate HCC from non-HCC tissue, a basic requirement for biomarker development trials. To assess that potential, we used quantitative Methylation Specific PCR, oligonucleotide tiling arrays, and Methylation BeadChip assays. Concurrent global DNA hypomethylation, gene-specific hypermethylation, and chromatin alterations were observed as a hallmark of HCC. A global loss of promoter methylation was observed in HCC with the Illumina BeadChip assays and the Nimblegen oligonucleotide arrays. HCC samples had lower median methylation peak scores and a reduced number of significant promoter-wide methylated probes. Promoter hypermethylation of RASSF1A, SSBP2, and B4GALT1 quantified by qMSP had a sensitivity ranging from 38% to 52%, a specificity of 100%, and an AUC from 0.58 to 0.75. A panel combining these genes with HCC risk factors had a sensitivity of 87%, a specificity of 100%, and an AUC of 0.91.http://dx.doi.org/10.1155/2014/597164 |
| spellingShingle | Christina Michailidi Ethan Soudry Mariana Brait Leonel Maldonado Andrew Jaffe Carmen Ili-Gangas Priscilla Brebi-Mieville Jimena Perez Myoung Sook Kim Xiaoli Zhong Quiang Yang Blanca Valle Stephen J. Meltzer Michael Torbenson Manel Esteller David Sidransky Rafael Guerrero-Preston Genome-Wide and Gene-Specific Epigenomic Platforms for Hepatocellular Carcinoma Biomarker Development Trials Gastroenterology Research and Practice |
| title | Genome-Wide and Gene-Specific Epigenomic Platforms for Hepatocellular Carcinoma Biomarker Development Trials |
| title_full | Genome-Wide and Gene-Specific Epigenomic Platforms for Hepatocellular Carcinoma Biomarker Development Trials |
| title_fullStr | Genome-Wide and Gene-Specific Epigenomic Platforms for Hepatocellular Carcinoma Biomarker Development Trials |
| title_full_unstemmed | Genome-Wide and Gene-Specific Epigenomic Platforms for Hepatocellular Carcinoma Biomarker Development Trials |
| title_short | Genome-Wide and Gene-Specific Epigenomic Platforms for Hepatocellular Carcinoma Biomarker Development Trials |
| title_sort | genome wide and gene specific epigenomic platforms for hepatocellular carcinoma biomarker development trials |
| url | http://dx.doi.org/10.1155/2014/597164 |
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