title: Comprehensive analyses of imprinted differentially methylated regions reveal epigenetic and genetic characteristics in hepatoblastoma.
abstract: BACKGROUND
  Aberrant methylation at imprinted differentially methylated regions (DMRs) in human 11p15.5 has been reported in many tumors including hepatoblastoma. However, the methylation status of imprinted DMRs in imprinted loci scattered through the human genome has not been analyzed yet in any tumors.
  
  
  METHODS
  The methylation statuses of 33 imprinted DMRs were analyzed in 12 hepatoblastomas and adjacent normal liver tissue by MALDI-TOF MS and pyrosequencing. Uniparental disomy (UPD) and copy number abnormalities were investigated with DNA polymorphisms.
  
  
  RESULTS
  Among 33 DMRs analyzed, 18 showed aberrant methylation in at least 1 tumor. There was large deviation in the incidence of aberrant methylation among the DMRs. KvDMR1 and IGF2-DMR0 were the most frequently hypomethylated DMRs. INPP5Fv2-DMR and RB1-DMR were hypermethylated with high frequencies. Hypomethylation was observed at certain DMRs not only in tumors but also in a small number of adjacent histologically normal liver tissue, whereas hypermethylation was observed only in tumor samples. The methylation levels of long interspersed nuclear element-1 (LINE-1) did not show large differences between tumor tissue and normal liver controls. Chromosomal abnormalities were also found in some tumors. 11p15.5 and 20q13.3 loci showed the frequent occurrence of both genetic and epigenetic alterations.
  
  
  CONCLUSIONS
  Our analyses revealed tumor-specific aberrant hypermethylation at some imprinted DMRs in 12 hepatoblastomas with additional suggestion for the possibility of hypomethylation prior to tumor development. Some loci showed both genetic and epigenetic alterations with high frequencies. These findings will aid in understanding the development of hepatoblastoma.
authors.forename: Janette Mareska
authors.initials: JM
authors.lastname: Rumbajan
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Maeda
authors.forename: Ryota
authors.initials: R
authors.lastname: Souzaki
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Mitsui
authors.forename: Ken
authors.initials: K
authors.lastname: Higashimoto
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakabayashi
authors.forename: Hitomi
authors.initials: H
authors.lastname: Yatsuki
authors.forename: Kenichi
authors.initials: K
authors.lastname: Nishioka
authors.forename: Ryoko
authors.initials: R
authors.lastname: Harada
authors.forename: Shigehisa
authors.initials: S
authors.lastname: Aoki
authors.forename: Kenichi
authors.initials: K
authors.lastname: Kohashi
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Oda
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Hata
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Saji
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Taguchi
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Tajiri
authors.affiliation: Department of Biomolecular Sciences, Division of Molecular Genetics & Epigenetics, Faculty of Medicine, Saga University, Nabeshima 5-1-1, Saga 849-8501, Japan. soejimah@cc.saga-u.ac.jp.
authors.forename: Hidenobu
authors.initials: H
authors.lastname: Soejima
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Joh
mesh_terms: D002648:Child; D002675:Child, Preschool; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D018392:Genomic Imprinting; D018197:Hepatoblastoma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007223:Infant; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D020084:Long Interspersed Nucleotide Elements; D008297:Male; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization