Methylation of drug resistance-related genes in chemotherapy-sensitive Epstein-Barr virus-associated gastric cancer

化疗敏感的EB病毒相关胃癌耐药相关基因甲基化

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作者:Hirofumi Ohmura, Mamoru Ito, Keita Uchino, Chihiro Okada, Shigeki Tanishima, Yuichi Yamada, Seiya Momosaki, Masato Komoda, Miyuki Kuwayama, Kyoko Yamaguchi, Yuta Okumura, Michitaka Nakano, Kenji Tsuchihashi, Taichi Isobe, Hiroshi Ariyama, Hitoshi Kusaba, Yoshinao Oda, Koichi Akashi, Eishi Baba

Abstract

Epstein-Barr virus (EBV)-associated gastric cancer (GC) is associated with a high degree of DNA methylation. However, the association between chemotherapy susceptibility and tumor DNA methylation in advanced diseases remains unclear. The comprehensive DNA methylation status of GC cells obtained from an advanced EBV-associated GC (EBVGC) case, in which complete response to S-1 plus cisplatin chemotherapy was achieved, was analyzed using a DNA methylation microarray. We compared DNA methylation of GC cells with public data and identified genes with higher methylation in EBVGC cell lines than in normal gastric cells, and genes in which methylation was increased by EBV. Of these genes, ABCG2, AHNAK2, BCL2, FZD1, and TP73 are associated with published evidence for resistance to 5-fluorouracil and cisplatin. Silencing of these genes may be associated with hypersensitivity to chemotherapy.

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