Biomedical subjects

Karl J Dykema

Publications and source records attributed to Karl J Dykema.

3 recordsLinked to original sources

PubMed2005

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.

COP9 Signalosome Complex↗

PubMed2005

Comparison of array-based comparative genomic hybridization with gene expression-based regional expression biases to identify genetic abnormalities in hepatocellular carcinoma.

BACKGROUND: Regional expression biases (REBs) are genetic intervals where gene expression is coordinately changed. For example, if a region of the genome is amplified, often the majority of genes that map within the amplified region show increased expression when compared to genes located in cytogenetically normal regions. As such, REBs have the potential to act as surrogates for cytogenetic data traditionally obtained using molecular technologies such as comparative genomic hybridization. However as REBs are identified using transcriptional information, detection of REBs may also identify local transcriptional abnormalities produced by both genetic and epigenetic mechanisms. RESULTS: REBs were identified from a set of hepatocellular carcinoma (HCC) gene expression profiles using a multiple span moving binomial test and compared to genetic abnormalities identified using array-based comparative genomic hybridization (aCGH). In the majority of cases, REBs overlapped genetic abnormalities as determined by aCGH. For example, both methods identified narrow regions of frequent amplification on chromosome 1p and narrow regions of frequent deletion on 17q. In a minority of cases, REBs were identified in regions not determined to be abnormal via other cytogenetic technologies. Specifically, expression biases reflective of cell proliferation were frequently identified on chromosome 6p21-23. CONCLUSION: Identification of REBs using a multiple span moving binomial test produced reasonable approximations of underlying cytogenetic abnormalities. However, caution should be used when attributing REBs identified on chromosome 6p to cytogenetic events in rapidly proliferating cells.

Carcinoma, Hepatocellular↗

PubMed2004

Diminished transcription of chromosome arm 4q is inversely related to local spreading of hepatocellular carcinoma.

To identify transcriptional features associated with local spreading of hepatocellular carcinoma (HCC), regional expression biases were determined from the gene expression profiles of solitary HCC tumors and of HCC tumors associated with additional intrahepatic lesions and/or portal vein involvement. Regional expression biases are genetic intervals in which gene expression is coordinately changed. Often, but not always, a regional expression bias indicates an underlying chromosomal aberration. This study demonstrated that the presence or absence of a regional expression bias on chromosome arm 4q can predict the presence or absence of intrahepatic spread/portal vein involvement in 83% of cases analyzed (n = 40). These results suggest that the transcriptional state of 4q may be a marker for local spreading of HCC and that a more detailed genetic/epigenetic characterization of this locus may provide additional insights into HCC development.

Carcinoma, Hepatocellular↗