Comprehensive analyses of imprinted differentially methylated regions reveal epigenetic and genetic characteristics in hepatoblastoma

Janette M. Rumbajan, Toshiyuki Maeda, Ryota Souzaki, Kazumasa Mitsui, Ken Higashimoto, Kazuhiko Nakabayashi, Hitomi Yatsuki, Kenichi Nishioka, Ryoko Harada, Shigehisa Aoki, Kenichi Kohashi, Yoshinao Oda, Kenichiro Hata, Tsutomu Saji, Tomoaki Taguchi, Tatsuro Tajiri, Hidenobu Soejima, Keiichiro Joh

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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.

Original languageEnglish
Article number608
JournalBMC Cancer
Volume13
DOIs
Publication statusPublished - Dec 27 2013

All Science Journal Classification (ASJC) codes

  • Genetics
  • Oncology
  • Cancer Research

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    Rumbajan, J. M., Maeda, T., Souzaki, R., Mitsui, K., Higashimoto, K., Nakabayashi, K., Yatsuki, H., Nishioka, K., Harada, R., Aoki, S., Kohashi, K., Oda, Y., Hata, K., Saji, T., Taguchi, T., Tajiri, T., Soejima, H., & Joh, K. (2013). Comprehensive analyses of imprinted differentially methylated regions reveal epigenetic and genetic characteristics in hepatoblastoma. BMC Cancer, 13, [608]. https://doi.org/10.1186/1471-2407-13-608