由Ricky Johnstone教授撰写Peter MacCallum Cancer Centre, Australia

On October 17 2013, the10^thNikko International Symposiumwas held at Jichi Medical University, Japan. The theme for this year’s symposium was Translational Epigenomics, with invited speakers from throughout Japan, selected speakers from Jichi Medical University and two invited international speakers, myself and Dr Omar Abdel-Wahab from Memorial Sloan-Kettering Cancer Centre, USA. Professor Keiya Ozawa, Director for the Center for Molecular Medicine, JichiS Medical University, was the convenor of the symposium and a gracious and energetic host.

A diverse array oforal presentationscovering fundamental, translational and clinical epigenetics/epigenomics was provided to an enthusiastic audience. Professor Yusuke Furukawa, Jichi Medical University, Japan, provided a contemporary update on the epigenetic reader, writer and eraser proteins that regulate the epigenome and the complex interplay between covalent modifications to histones and dynamic DNA methylation that regulates chromatin structure and gene transcription. This provided the perfect background for an intriguing talk given by Dr Taeko Wada, Jichi Medical University, Japan, who demonstrated the functional difference between long and short splice isoforms of LSD1. Dr Wada showed that the short LSD1 isoform produced following alternate splicing of exons 2 and 8 has higher affinity for the CoREST transcriptional cofactor, has enhanced demethylase activity and increases the self-renewal capacity of mouse LSK cells. Knockdown of this LSD1 isoform inhibited the growth of leukemic cells providing evidence for an oncogenic role for this form of LSD1. Dr Toshikazu Ushijima provided a provocative talk regarding the link between chronic inflammation caused byHelicobacter pylori(HP) infection and aberrant DNA methylation that results in a field effect termed “cancerization” by the author resulting in gastric cancer. Ushijima and colleagues have identified a gene set whose methylation levels distinguish gastric cancer patients from healthy individuals, even among individuals with pastHPinfection and pre-clinical studies demonstrated that 5-aza-dC preventedHP-induced gastric cancer.

Abdel-Wahab博士提出了杰出的演讲，他提供了一系列令人惊叹的实验，详细介绍了突变体ASXL1在髓样白血病发生中的作用。最初证明突变体ASXL1通过损失Polycomb抑制性复合物2（PRC2）介导的组蛋白H3赖氨酸27（H3K27）三甲基化具有致癌性，Abdel-Wahab博士介绍了有关条件性的最新数据asxl1-knockout mice. Deletion ofasxl1in hemopietic progenitor cells remarkably results in hypo-cellularity and multilineage dysplasia consistent with a bone marrow stem cell defect. Interestingly, crossingasxl1-knockout mice withTet2-deleted mice, that reflects the observation that somatic mutations inasxl1andTET2are often found in myeloid leukemias, resulted in enhanced bone marrow stem cell activity and hypercellularity. These studies demonstrated the important role of genetically engineered mice to decipher functional interactions between different epigenetic regulators and provided interesting insight into the role of PRC2 in myeloid transformation.

In summary the meeting highlighted the diversity and excellent standard of epigenetics research in Japan and the strong focus on translating basic findings into clinical practice. The symposium served to extend existing collaborations and initiate new ones and by all criteria was an outstanding success.

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