Genome-Wide and Gene-Specific Epigenomic Platforms for Hepatocellular Carcinoma Biomarker Development Trials

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

doi:10.1155/2014/597164

Gastroenterology Research and Practice (Jan 2014)

Genome-Wide and Gene-Specific Epigenomic Platforms for Hepatocellular Carcinoma Biomarker Development Trials

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

Affiliations

Christina Michailidi: Department of Otolaryngology, Division of Head and Neck Cancer Research, School of Medicine, The Johns Hopkins University, Baltimore, MD 21231, USA
Ethan Soudry: Department of Otolaryngology, Division of Head and Neck Cancer Research, School of Medicine, The Johns Hopkins University, Baltimore, MD 21231, USA
Mariana Brait: Department of Otolaryngology, Division of Head and Neck Cancer Research, School of Medicine, The Johns Hopkins University, Baltimore, MD 21231, USA
Leonel Maldonado: Department of Otolaryngology, Division of Head and Neck Cancer Research, School of Medicine, The Johns Hopkins University, Baltimore, MD 21231, USA
Andrew Jaffe: Department of Epidemiology, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, MD 21205, USA
Carmen Ili-Gangas: Department of Otolaryngology, Division of Head and Neck Cancer Research, School of Medicine, The Johns Hopkins University, Baltimore, MD 21231, USA
Priscilla Brebi-Mieville: Department of Otolaryngology, Division of Head and Neck Cancer Research, School of Medicine, The Johns Hopkins University, Baltimore, MD 21231, USA
Jimena Perez: Department of Otolaryngology, Division of Head and Neck Cancer Research, School of Medicine, The Johns Hopkins University, Baltimore, MD 21231, USA
Myoung Sook Kim: Department of Otolaryngology, Division of Head and Neck Cancer Research, School of Medicine, The Johns Hopkins University, Baltimore, MD 21231, USA
Xiaoli Zhong: Department of Otolaryngology, Division of Head and Neck Cancer Research, School of Medicine, The Johns Hopkins University, Baltimore, MD 21231, USA
Quiang Yang: Department of Otolaryngology, Division of Head and Neck Cancer Research, School of Medicine, The Johns Hopkins University, Baltimore, MD 21231, USA
Blanca Valle: Department of Otolaryngology, Division of Head and Neck Cancer Research, School of Medicine, The Johns Hopkins University, Baltimore, MD 21231, USA
Stephen J. Meltzer: Department of Gastroenterology, School of Medicine, The Johns Hopkins University, Baltimore, MD 21205, USA
Michael Torbenson: Department of Pathology, School of Medicine, The Johns Hopkins University, Baltimore, MD 21205, USA
Manel Esteller: Bellvitge Biomedical Research Institute, Barcelona, Catalonia, Spain
David Sidransky: Department of Otolaryngology, Division of Head and Neck Cancer Research, School of Medicine, The Johns Hopkins University, Baltimore, MD 21231, USA
Rafael Guerrero-Preston: Department of Otolaryngology, Division of Head and Neck Cancer Research, School of Medicine, The Johns Hopkins University, Baltimore, MD 21231, USA

DOI: https://doi.org/10.1155/2014/597164
Journal volume & issue: Vol. 2014

Abstract

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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.

Published in Gastroenterology Research and Practice

ISSN: 1687-6121 (Print); 1687-630X (Online)
Publisher: Hindawi Limited
Country of publisher: United Kingdom
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the digestive system. Gastroenterology
Website: https://onlinelibrary.wiley.com/journal/6480

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