TY - JOUR
T1 - Gene expression profiling reveals signatures characterizing histologic subtypes of hepatoblastoma and global deregulation in cell growth and survival pathways
AU - Adesina, Adekunle M.
AU - Lopez-Terrada, Dolores
AU - Wong, Kwong K.
AU - Gunaratne, Preethi
AU - Nguyen, Yummy
AU - Pulliam, Joseph
AU - Margolin, Judith
AU - Finegold, Milton J.
PY - 2009/6
Y1 - 2009/6
N2 - Hepatoblastoma is the most common malignant tumor of the liver of children worldwide. Histologically, hepatoblastomas show marked variation in the type and proportion of epithelial (fetal, embryonal, or small cell) and mesenchymal components with differing prognosis and response to therapy. The pure fetal-type hepatoblastoma, presenting as stage 1 and resectable, has the best prognosis, whereas the small cell histology has been associated with unfavorable outcome. Using gene expression profiling, we demonstrate that in addition to Wnt pathway deregulation, cell growth and survival pathways are also globally deregulated in hepatoblastomas. Furthermore, the different histologic subtypes are characterized by specific gene expression and pathway signatures that give insight into the degree of molecular heterogeneity that is present among these tumors. Although Wnt signaling pathway upregulation is common to all histologic types of hepatoblastoma, this pathway is even more significantly deregulated in aggressive hepatoblastomas. In addition, deregulation of MAPK signaling pathway and antiapoptotic signaling is preferentially upregulated in aggressive epithelial hepatoblastomas with a small cell component. The gene expression signatures reported here provide possible prognostic and diagnostic markers as well as therapeutic targets for this disease.
AB - Hepatoblastoma is the most common malignant tumor of the liver of children worldwide. Histologically, hepatoblastomas show marked variation in the type and proportion of epithelial (fetal, embryonal, or small cell) and mesenchymal components with differing prognosis and response to therapy. The pure fetal-type hepatoblastoma, presenting as stage 1 and resectable, has the best prognosis, whereas the small cell histology has been associated with unfavorable outcome. Using gene expression profiling, we demonstrate that in addition to Wnt pathway deregulation, cell growth and survival pathways are also globally deregulated in hepatoblastomas. Furthermore, the different histologic subtypes are characterized by specific gene expression and pathway signatures that give insight into the degree of molecular heterogeneity that is present among these tumors. Although Wnt signaling pathway upregulation is common to all histologic types of hepatoblastoma, this pathway is even more significantly deregulated in aggressive hepatoblastomas. In addition, deregulation of MAPK signaling pathway and antiapoptotic signaling is preferentially upregulated in aggressive epithelial hepatoblastomas with a small cell component. The gene expression signatures reported here provide possible prognostic and diagnostic markers as well as therapeutic targets for this disease.
KW - Fetal
KW - Gene expression profiling
KW - Liver tumors
KW - Pediatric
KW - Small cell and embryonal hepatoblastoma
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UR - http://www.scopus.com/inward/citedby.url?scp=67349252606&partnerID=8YFLogxK
U2 - 10.1016/j.humpath.2008.10.022
DO - 10.1016/j.humpath.2008.10.022
M3 - Article
C2 - 19200578
AN - SCOPUS:67349252606
SN - 0046-8177
VL - 40
SP - 843
EP - 853
JO - Human Pathology
JF - Human Pathology
IS - 6
ER -