Email updates

Keep up to date with the latest news and content from BMC Cancer and BioMed Central.

Open Access Highly Accessed Research article

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

Janette Mareska Rumbajan12, Toshiyuki Maeda1, Ryota Souzaki3, Kazumasa Mitsui4, Ken Higashimoto1, Kazuhiko Nakabayashi5, Hitomi Yatsuki1, Kenichi Nishioka1, Ryoko Harada4, Shigehisa Aoki6, Kenichi Kohashi7, Yoshinao Oda7, Kenichiro Hata5, Tsutomu Saji4, Tomoaki Taguchi3, Tatsuro Tajiri8, Hidenobu Soejima1* and Keiichiro Joh1*

Author Affiliations

1 Department of Biomolecular Sciences, Division of Molecular Genetics & Epigenetics, Faculty of Medicine, Saga University, Nabeshima 5-1-1, Saga 849-8501, Japan

2 Faculty of Medicine, Sam Ratulangi University, Manado, Indonesia

3 Department of Pediatric Surgery, Faculty of Medicine, Kyushu University, Fukuoka, Japan

4 Department of Pediatrics, Toho University, Omori Medical Center, Tokyo, Japan

5 Department of Maternal-Fetal Biology, National Research Institute for Child Health and Development, Tokyo, Japan

6 Department of Pathology and Microbiology, Division of Pathology, Faculty of Medicine, Saga University, Saga, Japan

7 Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

8 Department of Pediatric Surgery, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan

For all author emails, please log on.

BMC Cancer 2013, 13:608  doi:10.1186/1471-2407-13-608

Published: 27 December 2013

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.

Keywords:
Hepatoblastoma; Genomic imprinting; Differentially methylated region; DNA methylation