Loss of 13q is associated with genes involved in cell cycle and proliferation in dedifferentiated hepatocellular carcinoma.
Mod Pathol
; 21(12): 1479-89, 2008 Dec.
Article
em En
| MEDLINE
| ID: mdl-18820673
ABSTRACT
Dedifferentiation of hepatocellular carcinoma implies aggressive clinical behavior and is associated with an increasing number of genomic alterations, eg deletion of 13q. Genes directly or indirectly deregulated due to these genomic alterations are mainly unknown. Therefore this study compares array comparative genomic hybridization and whole genome gene expression data of 23 well, moderately, or poorly dedifferentiated hepatocellular carcinoma, using unsupervised hierarchical clustering. Dedifferentiated carcinoma clearly branched off from well and moderately differentiated carcinoma (P<0.001 chi(2)-test). Within the dedifferentiated group, 827 genes were upregulated and 33 genes were downregulated. Significance analysis of microarrays for hepatocellular carcinoma with and without deletion of 13q did not display deregulation of any gene located in the deleted region. However, 531 significantly upregulated genes were identified in these cases. A total of 6 genes (BIC, CPNE1, RBPMS, RFC4, RPSA, TOP2A) were among the 20 most significantly upregulated genes both in dedifferentiated carcinoma and in carcinoma with loss of 13q. These genes are involved in cell-cycle control and proliferation. Of 33 downregulated genes in the dedifferentiated subgroup, 4 metallothioneins had the lowest fold change, most probably mediated through inactivation of C/EBPalpha by the PI3K/AKT cascade. In conclusion dedifferentiation of hepatocellular carcinoma is associated with upregulation of genes involved in cell-cycle control and proliferation. Notably, a significant portion of these genes is also upregulated in carcinoma with deletion of 13q. As no downregulated genes were identified and microRNAs (mir-621, mir-16-1, mir-15a) are located within the deleted region of 13q and may be lost, we speculate that these miRNAs may induce the upregulation of critical cell-cycle control genes.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cromossomos Humanos Par 13
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Ciclo Celular
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Carcinoma Hepatocelular
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Neoplasias Hepáticas
Tipo de estudo:
Risk_factors_studies
Limite:
Adult
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Aged
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Child
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article