@article {NIINUMA2817, author = {TAKESHI NIINUMA and HIROSHI KITAJIMA and EIICHIRO YAMAMOTO and REO MARUYAMA and HIRONORI AOKI and TAKU HARADA and KAZUYA ISHIGURO and GOTA SUDO and MUTSUMI TOYOTA and AYANO YOSHIDO and MASAHIRO KAI and HIROSHI NAKASE and TAMOTSU SUGAI and HIROMU SUZUKI}, title = {An Integrated Epigenome and Transcriptome Analysis to Clarify the Effect of Epigenetic Inhibitors on GIST}, volume = {41}, number = {6}, pages = {2817--2828}, year = {2021}, doi = {10.21873/anticanres.15062}, publisher = {International Institute of Anticancer Research}, abstract = {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.}, issn = {0250-7005}, URL = {https://ar.iiarjournals.org/content/41/6/2817}, eprint = {https://ar.iiarjournals.org/content/41/6/2817.full.pdf}, journal = {Anticancer Research} }