Digestive diseases (Basel, Switzerland) · 2014
Genome-wide profiling of DNA methylation and tumor progression in human hepatocellular carcinoma.
Сравнительное исследованиеСтатьяНазвание и аннотация: Перевод в очереди
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Nishida Naoshi, Nishimura Takafumi, Nakai Takuya, Chishina Hirokazu, Arizumi Tadaaki, Takita Masahiro, Kitai Satoshi, Yada Norihisa, Hagiwara Satoru, Inoue Tatsuo, Minami Yasunori, Ueshima Kazuomi, Sakurai Toshiharu, Kudo Masatoshi
Аннотация
OBJECTIVE: To clarify the progression pattern of abnormal DNA methylation during the development of hepatocellular carcinoma (HCC) using a comprehensive methylation assay.
METHODS: We used an Infinium HumanMethylation450 BeadChip array that can analyze >485,000 CpG sites distributed throughout the genome for a comprehensive methylation study of 117 liver tissues consisting of 59 HCC and 58 noncancerous livers. Altered DNA methylation patterns during tumor progression were also analyzed.
RESULTS: We identified 38,330 CpG sites with significant differences in methylation levels between HCCs and noncancerous livers (DM-CpGs) using strict criteria. Of the DM-CpGs, 92% were hypomethylated and only 3,051 CpGs (8%) were hypermethylated in HCC. The DM-CpGs were more prevalent within intergenic regions with isolated CpGs. In contrast, DM-CpGs that were hypermethylated in HCC were predominantly located within promoter regions and CpG islands (p < 0.0001). The association between methylation profiles of DM-CpGs and tumor size was statistically significant, especially in hepatitis C virus (HCV)-positive cases (p = 0.0001).
CONCLUSIONS: We clarified the unique characteristics of DM-CpGs in human HCCs. The stepwise progression of alterations in DNA methylation was a common feature of HCV-related hepatocarcinogenesis.
METHODS: We used an Infinium HumanMethylation450 BeadChip array that can analyze >485,000 CpG sites distributed throughout the genome for a comprehensive methylation study of 117 liver tissues consisting of 59 HCC and 58 noncancerous livers. Altered DNA methylation patterns during tumor progression were also analyzed.
RESULTS: We identified 38,330 CpG sites with significant differences in methylation levels between HCCs and noncancerous livers (DM-CpGs) using strict criteria. Of the DM-CpGs, 92% were hypomethylated and only 3,051 CpGs (8%) were hypermethylated in HCC. The DM-CpGs were more prevalent within intergenic regions with isolated CpGs. In contrast, DM-CpGs that were hypermethylated in HCC were predominantly located within promoter regions and CpG islands (p < 0.0001). The association between methylation profiles of DM-CpGs and tumor size was statistically significant, especially in hepatitis C virus (HCV)-positive cases (p = 0.0001).
CONCLUSIONS: We clarified the unique characteristics of DM-CpGs in human HCCs. The stepwise progression of alterations in DNA methylation was a common feature of HCV-related hepatocarcinogenesis.