Expression of genes involved with cell cycle control, cell growth and chromatin modification are altered in hepatoblastomas.
Hepatoblastoma is a rare pediatric liver tumor. While much progress has been made in the treatment of the disease, very little is known about the moleculer events underlying the pathogenesis of this disease. We sought to investigate a series of hepatoblastomas for alterations in gene expression patterns with emphasis on important cell regulatory genes, including chromatin modifying enzymes, cyclin dependent kinase inhibitors, growth factors, oncogenes and cell cycle regulators. Total RNA was extracted from a series of sporadic hepatoblastomas with matched normal liver, some unmatched tumors and fetal livers, and gene expression was measured for various genes using RNase Protection Analysis (RPA). The results of this analysis show that the expression of many important regulatory genes are distinctly altered in these tumors, and a subset of tumors can be distinguished on the basis of these gene expression differences and histopathological features. Because the molecular events underlying the pathogenesis of this rare tumor are so poorly understood, this study represents a first step in determining some of the possible mechanisms involved which may provide future avenues of research.
Gray
S G
SG
Laboratory for Molecular Development and Tumor Biology, Experimental Alcohol and Drug Addiction Research Section, Department of Clinical Neuroscience, Karolinska Institute, CMM L8:01, S-171 76 Stockholm, Sweden.
Hartmann
W
W
Eriksson
T
T
Ekstrom
C
C
Holm
S
S
Kytola
S
S
von Schweinitz
D
D
Pietsch
T
T
Larsson
C
C
Kogner
P
P
Sandstedt
B
B
Ekstrom
T J
TJ
D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002675:Child, Preschool; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D016161:Genes, Retinoblastoma / Q000502:physiology; D016158:Genes, p53 / Q000502:physiology; D018197:Hepatoblastoma / Q000235:genetics* / Q000473:pathology; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007223:Infant; D008099:Liver / Q000196:embryology / Q000502:physiology; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D011519:Proto-Oncogenes / Q000235:genetics / Q000502:physiology; D015347:RNA Probes; D012016:Reference Values; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
D018797:Cell Cycle Proteins; D004791:Enzyme Inhibitors; D015347:RNA Probes; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D018844:Cyclin-Dependent Kinases; D006655:Histone Deacetylases