Integrative array-based approach identifies MZB1 as a frequently methylated putative tumor suppressor in hepatocellular carcinoma

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Satoshi MatsumuraJohji Inazawa

Abstract

The aim of this study was the identification of novel tumor suppressor genes (TSG) silenced by DNA hypermethylation in hepatocellular carcinoma (HCC). We conducted integrative array-based approach for genome-wide screening of methylation targets using a methylated DNA immunoprecipitation-CpG island microarray and expression array in three universal hepatoma cell lines and normal liver tissue. Through detailed expression and functional analyses using hepatoma cell lines and primary HCC samples, we isolated novel TSGs for HCC. A total of 642 genes were identified as methylated in three hepatoma cell lines but unmethylated in normal liver tissue, whereas 204 genes on autosomes were identified as genes unexpressed but restored after treatment with 5-aza-2'-deoxycytidine in these cell lines and expressed in normal tissue. Through the integration of results of the two-array analyses and further validation analyses of expression and methylation status in 17 cell lines and 30 primary tumors of hepatoma, we identified MZB1, marginal zone B and B1 cell-specific protein, encoding an endoplasmic reticulum protein, as a putative TSG frequently methylated within its CpG island in hepatoma. Among 162 patients with primary HCC, silencing of MZ...Continue Reading

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Citations

Jun 21, 2014·BioMed Research International·Rengjing ZhangXiaobo Zhou
Jul 28, 2016·International Journal of Cancer. Journal International Du Cancer·Mitsuro KandaYasuhiro Kodera
Mar 19, 2014·Biomarker Research·Way-Champ Mah, Caroline Gl Lee
Jan 10, 2017·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Jiliang QiuYunfei Yuan
Mar 7, 2021·International Journal of Molecular Sciences·Hao Wei, Ji-Yang Wang

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