Carcinogenesis Advance Access originally published online on July 6, 2005
Carcinogenesis 2005 26(12):2050-2057; doi:10.1093/carcin/bgi178
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Carcinogenesis Vol.26 No.12 © Oxford University Press 2005; all rights reserved.
Array-based comparative genomic hybridization reveals recurrent chromosomal aberrations and Jab1 as a potential target for 8q gain in hepatocellular carcinoma
1 Department of Biopharmaceutical Sciences, 2 Department of Pathology, 3 Cancer Center and 4 Liver Center, University of California, San Francisco, CA 94143, USA, 5 Department of Pathology, University of Bonn, Bonn, Germany, 6 Department of Surgery, Beijing Cancer Hospital, Peking University School of Oncology, Beijing, China, 7 Department of Surgery and Center for the Study of Liver Disease, The University of Hong Kong, Hong Kong, China, 8 Department of Surgery and Asian Liver Center, Stanford University, Stanford, CA 94305, USA and 9 Bioinformatics Special Program, Van Andel Research Institute, Grand Rapids, MI 49503, USA
* To whom correspondence should be addressed. Tel: 415 502 6526; Fax: 415 502 4322; E-mail: chenx{at}pharmacy.ucsf.edu
Hepatocellular carcinoma (HCC) is one of the major malignancies worldwide. We have previously characterized global gene expression patterns in HCC using microarrays. Here, we report the analysis of genomic DNA copy number among 49 HCC samples using BAC array-based comparative genomic hybridization (CGH). We observed recurrent and characteristic chromosomal aberrations, including frequent DNA copy number gains of 1q, 6p, 8q and 20q, and losses of 4q, 8p, 13q, 16q and 17p. We correlated gene expression with array CGH data, and identified a set of genes whose expression levels correlated with common chromosomal aberrations in HCC. Especially, we noticed that high expression of Jab1 in HCC significantly correlated with DNA copy number gain at 8q. Quantitative microsatellite analysis further confirmed DNA copy number gain at the Jab1 locus. Overexpression of Jab1 in HCC was also validated using real-time RT–PCR, and Jab1 protein levels were studied by immunohistochemistry on tissue microarrays. Functional analysis in HCC cell lines demonstrated that Jab1 may regulate HCC cell proliferation, thereby having a potential role in HCC development. In conclusion, this study shows that array-based CGH provides high resolution mapping of chromosomal aberrations in HCC, and demonstrates the feasibility of correlating array CGH data with gene expression data to identify novel oncogenes and tumor suppressor genes.
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