FOXG1 is overexpressed in hepatoblastoma.
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.
Adesina
Adekunle Michael
AM
Department of Pathology, Texas Children's Hospital, Baylor College of Medicine, Houston, TX 77030, USA. aadesina@bcm.tmc.edu
Nguyen
Yummy
Y
Guanaratne
Preethi
P
Pulliam
Joseph
J
Lopez-Terrada
Dolores
D
Margolin
Judy
J
Finegold
Milton
M
D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis; D051858:Forkhead Transcription Factors / Q000096:biosynthesis*; D018197:Hepatoblastoma / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism*; D011493:Protein Kinase C / Q000096:biosynthesis; D015854:Up-Regulation
D050759:Cyclin-Dependent Kinase Inhibitor p21; D051858:Forkhead Transcription Factors; C089212:protein kinase D; D011493:Protein Kinase C