RT Journal Article
SR Electronic
T1 An Integrated Epigenome and Transcriptome Analysis to Clarify the Effect of Epigenetic Inhibitors on GIST
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 2817
OP 2828
DO 10.21873/anticanres.15062
VO 41
IS 6
A1 TAKESHI NIINUMA
A1 HIROSHI KITAJIMA
A1 EIICHIRO YAMAMOTO
A1 REO MARUYAMA
A1 HIRONORI AOKI
A1 TAKU HARADA
A1 KAZUYA ISHIGURO
A1 GOTA SUDO
A1 MUTSUMI TOYOTA
A1 AYANO YOSHIDO
A1 MASAHIRO KAI
A1 HIROSHI NAKASE
A1 TAMOTSU SUGAI
A1 HIROMU SUZUKI
YR 2021
UL http://ar.iiarjournals.org/content/41/6/2817.abstract
AB Background/Aim: Epigenetic alterations play an important role in the pathogenesis of gastrointestinal stromal tumors (GISTs). To obtain further insight into the GIST epigenome, we analyzed genome-wide histone modification and DNA methylation in GIST cells. Materials and Methods: To reverse epigenetic silencing, GIST-T1 cells were treated with a DNA methyltransferase inhibitor and a histone deacetylase inhibitor, and subsequently H3K4me3 levels, the DNA methylome, and the transcriptome were analyzed. Results: Treatment with epigenetic inhibitors not only up-regulated genes with DNA methylation, but also genes related to interferon signaling. ChIP-seq analysis revealed that drug treatment up-regulated H3K4me3 levels in retrotransposons, including endogenous retroviruses (ERV). Finally, utilizing the omics data, we found that hypermethylation of MEG3 is a frequent event and an indicator of poorer prognosis in GIST patients. Conclusion: Epigenetic inhibitors may activate interferon signaling via viral mimicry in GIST cells. Moreover, epigenome data could be a useful resource to identify novel GIST-related genes.