Differential gene alteration among hepatoma cell lines demonstrated by cDNA microarray-based comparative genomic hybridization.
We assayed chromosomal abnormalities in hepatoma cell lines using the microarray-based comparative genomic hybridization (array-CGH) method and investigated the relationship between genomic copy number alterations and expression profiles in these hepatoma cell lines. We modified a cDNA array-CGH assay to compare genomic DNAs from seven hepatoma cell lines, as well as DNA from two non-hepatoma cell lines and from normal cells. The mRNA expression of each sample was assayed in parallel by cDNA microarray. We identified small amplified or deleted chromosomal regions, as well as alterations in DNA copy number not previously described. We predominantly found alterations of apoptosis-related genes in Hep3B and HepG2, cell adhesion and receptor molecules in HLE, and cytokine-related genes in PLC/PRF/5. About 40% of the genes showing amplification or loss showed altered levels of mRNA (p < 0.05). Hierarchical clustering analysis showed that the expression of these genes allows differentiation between alpha-fetoprotein (AFP)-producing and AFP-negative cell lines. cDNA array-CGH is a sensitive method that can be used to detect alterations in genomic copy number in tumor cells. Differences in DNA copy alterations between AFP-producing and AFP-negative cells may lead to differential gene expression and may be related to the phenotype of these cells.
Kawaguchi
Kazunori
K
Department of Gastroenterology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
Honda
Masao
M
Yamashita
Taro
T
Shirota
Yukihiro
Y
Kaneko
Shuichi
S
D017209:Apoptosis; D015139:Blotting, Southern; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002874:Chromosome Mapping; D016000:Cluster Analysis; D018076:DNA, Complementary / Q000378:metabolism; D017353:Gene Deletion; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D010641:Phenotype; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D000509:alpha-Fetoproteins / Q000378:metabolism
D018076:DNA, Complementary; D012333:RNA, Messenger; D000509:alpha-Fetoproteins