Array-based comparative genomic hybridization reveals recurrent chromosomal aberrations and Jab1 as a potential target for 8q gain in hepatocellular carcinoma.
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.
Department of Biopharmaceutical Sciences, University of California, San Francisco, CA 94143, USA.
Mohini A
MA
Patil
Ines
I
Gütgemann
Ji
J
Zhang
Coral
C
Ho
Siu-Tim
ST
Cheung
David
D
Ginzinger
Rui
R
Li
Karl J
KJ
Dykema
Samuel
S
So
Sheung-Tat
ST
Fan
Sanjay
S
Kakar
Kyle A
KA
Furge
Reinhard
R
Büttner
Xin
X
Chen
D000075686:COP9 Signalosome Complex; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D002869:Chromosome Aberrations; D022202:Chromosomes, Artificial, Bacterial; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D005784:Gene Amplification; D018628:Gene Dosage; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000235:genetics*; D007621:Karyotyping; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D046228:Microarray Analysis; D018895:Microsatellite Repeats; D009364:Neoplasm Recurrence, Local; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D010447:Peptide Hydrolases / Q000235:genetics*; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014407:Tumor Cells, Cultured
D047908:Intracellular Signaling Peptides and Proteins; D034741:RNA, Small Interfering; D010447:Peptide Hydrolases; C501488:COPS5 protein, human; D000075686:COP9 Signalosome Complex