Journal Article

Array-based comparative genomic hybridization reveals recurrent chromosomal aberrations and Jab1 as a potential target for 8q gain in hepatocellular carcinoma

Mohini A. Patil, Ines Gütgemann, Ji Zhang, Coral Ho, Siu-Tim Cheung, David Ginzinger, Rui Li, Karl J. Dykema, Samuel So, Sheung-Tat Fan, Sanjay Kakar, Kyle A. Furge, Reinhard Büttner and Xin Chen

in Carcinogenesis

Volume 26, issue 12, pages 2050-2057
Published in print December 2005 | ISSN: 0143-3334
Published online July 2005 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgi178
Array-based comparative genomic hybridization reveals recurrent chromosomal aberrations and Jab1 as a potential target for 8q gain in hepatocellular carcinoma

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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.

Keywords: BAC, bacterial artificial chromosome; CGH, comparative genomic hybridization; CSN5, COP9 constitutive photomorphogenic homolog subunit 5; HCC, hepatocellular carcinoma; Jab1, Jun activation domain binding protein; QuMA: quantitative microsatellite analysis; SAM, significant analysis of microarray; TMA, tissue-microarray

Journal Article.  5811 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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