TY - JOUR
T1 - Comprehensive analyses of imprinted differentially methylated regions reveal epigenetic and genetic characteristics in hepatoblastoma
AU - Rumbajan, Janette M.
AU - Maeda, Toshiyuki
AU - Sozaki, Ryota
AU - Mitsui, Kazumasa
AU - Higashimoto, Ken
AU - Nakabayashi, Kazuhiko
AU - Yatsuki, Hitomi
AU - Nishioka, Kenichi
AU - Harada, Ryoko
AU - Aoki, Shigehisa
AU - Kohashi, Kenichi
AU - Oda, Yoshinao
AU - Hata, Kenichiro
AU - Saji, Tsutomu
AU - Taguchi, Tomoaki
AU - Tajiri, Tatsuro
AU - Soejima, Hidenobu
AU - Joh, Keiichiro
N1 - Funding Information:
We thank Prof. Yutaka Kondo, Division of Epigenomics, Aichi Cancer Center Research Institute, Japan for technical advices in LINE-1 methylation analysis. This study was supported, in part, by a Grant for Research on Intractable Diseases from the Ministry of Health, Labor, and Welfare; a Grant for Child Health and Development from the National Center for Child Health and Development; and, a Grant-in-Aid for Challenging Exploratory Research and a Grant-in-Aid for Young Scientists (B) from the Japan Society for the Promotion of Science.
PY - 2013/12/27
Y1 - 2013/12/27
N2 - 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.
AB - 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.
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U2 - 10.1186/1471-2407-13-608
DO - 10.1186/1471-2407-13-608
M3 - Article
C2 - 24373183
AN - SCOPUS:84891010570
SN - 1471-2407
VL - 13
JO - BMC Cancer
JF - BMC Cancer
M1 - 608
ER -
