Transcriptional profiling in hepatoblastomas using high-density oligonucleotide DNA array.
Hepatoblastoma is a common hepatic tumor in children. Although evidence regarding cytogenetic and molecular genetic alterations in hepatoblastomas has been reported, the molecular events affecting the biologic characteristics of this tumor, including alterations of the gene expression profile, are largely unknown. To identify genes differentially expressed between nondiseased liver (NDL) and hepatoblastoma tumor (HBT), we analyzed the gene expression profile in 14 NDL and 16 HBT samples using a high-density oligonucleotide DNA array. Using Mann-Whitney U test followed by the k-nearest neighbor algorithm, we identified 26 genes (predictor genes) that were able to assign unknown samples derived from NDL and HBT to either the NDL group or HBT group with 100% accuracy. Using a cross-validation approach, we confirmed that the k-nearest neighbor algorithm assigned the particular samples derived from NDL and HBT to either the NDL or HBT group with 93.3% (28/30 samples) accuracy. In the 26 predictor genes, we found alteration of the expression of genes regulating cell division (NAP1L1, STMN1, CCNG2, and CDC7L1) and tumor cell growth (IGF2 and IGFBP4) in HBT. Four predictor genes (ETV3, TPR, CD34, and NR1I3) were also found to be mapped to the chromosomal region 1q21 approximately q32, which has been reported to be frequently involved in the development of hepatoblastoma. The findings obtained in this study suggest that alteration of the expression of some genes regulating cell division and tumor cell growth may be characteristics of the gene expression profile in HBT, and that alteration of the expression of the four predictor genes mapped to chromosomal region 1q21 approximately q32 may also contribute to the differences in gene expression profile between NDL and HBT.
Nagata
Toshihito
T
Department of Advanced Medicine, Nihon University, School of Medicine, 30-1 Oyaguchikami-cho, Itabashi-ku, Tokyo 173-8610, Japan. tnagata@med.nihon-u.ac.jp
Takahashi
Yasuo
Y
Ishii
Yukimoto
Y
Asai
Satoshi
S
Nishida
Yayoi
Y
Murata
Akiko
A
Koshinaga
Tsugumichi
T
Fukuzawa
Masahiro
M
Hamazaki
Minoru
M
Asami
Keiko
K
Ito
Etsuro
E
Ikeda
Hitoshi
H
Takamatsu
Hideo
H
Koike
Kenichi
K
Kikuta
Atsushi
A
Kuroiwa
Minoru
M
Watanabe
Arata
A
Kosaka
Yoshiyuki
Y
Fujita
Hiroo
H
Miyake
Munenori
M
Mugishima
Hideo
H
D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D000090702:Constitutive Androstane Receptor; D005260:Female; D020869:Gene Expression Profiling; D018197:Hepatoblastoma / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D010802:Phylogeny
D000090702:Constitutive Androstane Receptor; C000716327:NR1I3 protein, human; D007335:Insulin-Like Growth Factor II