FOXG1 is overexpressed in hepatoblastoma
ABSTRACT Bacterial artificial chromosome array comparative genomic hybridization analysis of hepatoblastomas reveals a deletion in the 14q12 locus in 12 of 16 cases. A high frequency of copy gain is seen on chromosomes 1q, 2, 5p, 8, and 20. Frequent deletions are also seen at 6q, 17q, and 1p with less frequent gains on 4p, 6p, and 19p. 14q12 deletion locus analyses using quantitative real-time polymerase chain reaction reveals copy number gain/amplification in the region immediately telomeric to the deleted locus, including copy number gain (2- to 4-fold) of FOXG1 in 13 out of 16 tumors. This is associated with up-regulation (approximately 87-fold) of FOXG1 gene transcripts and increased protein expression. Immunostaining reveals an inverse relationship between FOXG1 expression and p21cip1 expression in all histologic subtypes. However, FOXG1 transcript levels were significantly higher (approximately 75-fold) in tumors with embryonal and small cell components when compared with pure fetal hepatoblastomas. FOXG1 has been implicated in the repression of transforming growth factor beta-induced expression of p21cip1 and cytostasis. Our findings are consistent with such a role for FOXG1. We propose that FOXG1 overexpression may contribute to the maintenance of the undifferentiated state in hepatoblastomas and could be a potential target for molecular therapeutics. This is the first report of a possible role for FOXG1 in hepatoblastoma and pediatric neoplasia.
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ABSTRACT: Evidence from a variety of sources suggests that structural alterations in the brain, including neurogenesis, may play a role in both the pathogenesis of mood disorders and the mechanism of action of antidepressants. Previous studies have implicated both the transforming growth factor-beta (TGF-beta), and the phosphatidyl inositol-3 kinase (PI3K)-Akt pathways in the neurogenesis-promoting and behavioral properties of antidepressants. Forkhead box protein G1 (FoxG1) is a major regulator of both of these pathways, and FoxG1 heterozygous null mice (FoxG1+/-) have previously been reported to have deficits in adult hippocampal neurogenesis and behavioral abnormalities including deficits in contextual fear learning. However the role of FoxG1, if any, in the response to antidepressants has not been previously investigated.To investigate the role of the FoxG1 gene in the behavioral and neurogenic properties of antidepressants, we tested FoxG1+/- mice and littermate controls in two different rodent models of antidepressant action: the tail suspension test and the forced swim test. FoxG1+/- mice showed no response to antidepressants in either of these tests. These results suggest that normal levels of FoxG1 may be required for the behavioral response to antidepressants.Synapse 02/2010; 64(2):169-71. DOI:10.1002/syn.20737 · 2.43 Impact Factor
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ABSTRACT: We report a rare case of hepatic carcinosarcoma consisting of two carcinomatous components and four sarcomatous components. A 54-year-old Japanese man presented with sudden right upper abdominal pain. Computed tomography showed a hepatic tumor measuring 17cm in the greatest dimension and intractable ascites, suggesting rupture of hepatocellular carcinoma (HCC). Transcatheter arterial embolization was repeated at our hospital, resulting in stabilization of the patient’s general condition. Right anterior and left median sectionectomies were performed. Histologically, the tumor consisted of carcinomatous and sarcomatous elements. The carcinomatous elements consisted of moderately differentiated HCC (positive for hepatocyte antibody, murine monoclonal anti-cytokeratin antibody, and alpha-fetoprotein and negative for S-100 and desmin) and adenocarcinoma (negative for cytokeratin 7 and positive for carcinoembryonic antigen). Sarcomatous elements consisted of undifferentiated spindle cell sarcoma, rhabdomyosarcoma with acidophil striated cells including striped cells (desmin-positive), chondrosarcoma with cartilage matrix (S-100-positive), and osteosarcoma with osteoid. The sarcomatous elements were negative for epithelial markers. The patient is alive at 34months after the operation with peritoneal dissemination. A total of 23 cases, including the present case, of hepatic carcinosarcoma have been reported in the English language literature. This is the third reported case of hepatic carcinosarcoma with heterogeneous carcinomatous and sarcomatous elements. KeywordsHepatic carcinosarcoma-HCC-Rhabdomyosarcoma-Chondrosarcoma-OsteosarcomaClinical Journal of Gastroenterology 04/2010; 3(2):97-103. DOI:10.1007/s12328-010-0138-0