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.


CONCLUSIONS
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.
Furge
Kyle A
KA
Van Andel Research Institute, 333 Bostwick Ave. NE, Grand Rapids, MI 49503, USA. kyle.furge@vai.org
Dykema
Karl J
KJ
Ho
Coral
C
Chen
Xin
X
D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000235:genetics*; D049109:Cell Proliferation; D002869:Chromosome Aberrations; D002886:Chromosomes, Human, Pair 17; D002896:Chromosomes, Human, Pair 6; D003627:Data Interpretation, Statistical; D017353:Gene Deletion; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism; D015233:Models, Statistical; D009693:Nucleic Acid Hybridization / Q000379:methods*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D014158:Transcription, Genetic