Comprehensive analyses of imprinted differentially methylated regions reveal epigenetic and genetic characteristics in hepatoblastoma
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
BMC Cancer 2013, 13:608 doi:10.1186/1471-2407-13-608Published: 27 December 2013
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.
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.
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.
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.