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Annual Report 2018

Division of Translational Informatics

Katsuya Tsuchihara, Riu Yamashita, Hideki Makinoshima, Sachiyo Mimaki, Yukie Kashima, Rumi Fujioka, Megumi Iwakura, Hiroko Kumakura, Keita Saito, Junyang Du, Yamato Hamaya, Yumi Hakozaki, Hiroyasu Esumi, Yutaka Suzuki, Mai Orii, Ayako Suzuki, Atsushi Yagishita, Tatsunosuke Ikemura, Keita Masuzawa, Joji Nakayama, Tomoyuki Miyashita, Ami Maruyama

Introduction

 It is necessary to obtain high-quality clinical information for cancer research. In addition, multi-omics data from patient specimens and model systems are indispensable to investigate the carcinogenic mechanism and the effects of therapeutic drugs. Several new multi-omics technologies such as single-cell analysis and microbiome analysis have been developed in recent years, and clinical sequence platforms enable us to obtain a large amount of omics-data with clinical information. Not only clinical and biological knowledge but also bioinformatics which extract meaningful information effectively is essential to integrate and analyze those data.

The Team and What We Do

 The Division of Translational Informatics is designing an efficient pipeline for data processing and constructing web database servers for user convenience.

Research activities

 Significant alterations of nucleotide metabolism in small-cell lung carcinoma cells were identified and higher amounts of purine-related aqueous metabolites such as hypoxanthine were relevant to resistance to PI3K pathway inhibition. SCRUM-Japan data center has been integrating clinical and genome data of more than 10,000 cases. All the accumulated genome data were reviewed and fixed for further research use.

Clinical trials

 Screening project for individualized medicine in Japan (SCRUM-Japan): Data center.

Education

 Our division accepted and trained the following trainees: Graduate students from the University of Tokyo, staff physicians and residents of Keio University.

Future prospects

 Development of new technologies that integrate clinical and multi-omics data will be more important and necessary to move forward cancer research and drug development. Supplying well trained translational informaticians with various backgrounds is also needed.

List of papers published in 2018

Journal

 1. Seki M, Katsumata E, Suzuki A, Sereewattanawoot S, Sakamoto Y, Mizushima-Sugano J, Sugano S, Kohno T, Frith MC, Tsuchihara K, Suzuki Y. Evaluation and application of RNA-Seq by Min- ION. DNA Res, 26:55-65, 2019

 2. Sugawara J, Ochi D, Yamashita R, Yamauchi T, Saigusa D, Wagata M, Obara T, Ishikuro M, Tsunemoto Y, Harada Y, Shibata T, Mimori T, Kawashima J, Katsuoka F, Igarashi-Takai T, Ogishima S, Metoki H, Hashizume H, Fuse N, Minegishi N, Koshiba S, Tanabe O, Kuriyama S, Kinoshita K, Kure S, Yaegashi N, Yamamoto M, Hiyama S, Nagasaki M. Maternity Log study: a longitudinal lifelog monitoring and multiomics analysis for the early prediction of complicated pregnancy. BMJ Open, 9:e025939, 2019

 3. Nakasone S, Mimaki S, Ichikawa T, Aokage K, Miyoshi T, Sugano M, Kojima M, Fujii S, Kuwata T, Ochiai A, Tsuboi M, Goto K, Tsuchihara K, Ishii G. Podoplanin-positive cancer-associated fibroblast recruitment within cancer stroma is associated with a higher number of single nucleotide variants in cancer cells in lung adenocarcinoma. J Cancer Res Clin Oncol, 144:893-900, 2018

 4. Makinoshima H, Umemura S, Suzuki A, Nakanishi H, Maruyama A, Udagawa H, Mimaki S, Matsumoto S, Niho S, Ishii G, Tsuboi M, Ochiai A, Esumi H, Sasaki T, Goto K, Tsuchihara K. Metabolic Determinants of Sensitivity to Phosphatidylinositol 3-Kinase Pathway Inhibitor in Small-Cell Lung Carcinoma. Cancer Res, 78:2179-2190, 2018

 5. Yamazaki S, Higuchi Y, Ishibashi M, Hashimoto H, Yasunaga M, Matsumura Y, Tsuchihara K, Tsuboi M, Goto K, Ochiai A, Ishii G. Collagen type I induces EGFR-TKI resistance in EGFR-mutated cancer cells by mTOR activation through Akt-independent pathway. Cancer Sci, 109:2063-2073, 2018

 6. Kageyama SI, Nihei K, Karasawa K, Sawada T, Koizumi F, Yamaguchi S, Kato S, Hojo H, Motegi A, Tsuchihara K, Akimoto T. Radiotherapy increases plasma levels of tumoral cell-free DNA in non-small cell lung cancer patients. Oncotarget, 9:19368-19378, 2018

 7. Sunami K, Takahashi H, Tsuchihara K, Takeda M, Suzuki T, Naito Y, Sakai K, Dosaka-Akita H, Ishioka C, Kodera Y, Muto M, Wakai T, Yamazaki K, Yasui W, Bando H, Fujimoto Y, Fukuoka S, Harano K, Kawazoe A, Kimura G, Koganemaru S, Kogawa T, Kotani D, Kuboki Y, Matsumoto H, Matsumoto S, Mishima S, Nakamura Y, Sawada K, Shingaki S, Shitara K, Umemoto K, Umemura S, Yasuda K, Yoshino T, Yamamoto N, Nishio K. Clinical practice guidance for next-generation sequencing in cancer diagnosis and treatment (Edition 10). Cancer Sci, 109:2980-2985, 2018

 8. Yamazaki K, Taniguchi H, Yoshino T, Akagi K, Ishida H, Ebi H, Nakatani K, Muro K, Yatabe Y, Yamaguchi K, Tsuchihara K. Japanese Society of Medical Oncology Clinical Guidelines: Molecular Testing for Colorectal Cancer Treatment, Third Edition. Cancer Sci, 109:2074-2079, 2018

 9. Ohta T, Kawashima T, Shinozaki NO, Dobashi A, Hiraoka S, Hoshino T, Kanno K, Kataoka T, Kawashima S, Matsui M, Nemoto W, Nishijima S, Suganuma N, Suzuki H, Taguchi YH, Takenaka Y, Tanigawa Y, Tsuneyoshi M, Yoshitake K, Sato Y, Yamashita R, Arakawa K, Iwasaki W. Collaborative environmental DNA sampling from petal surfaces of flowering cherry Cerasus x yedoensis 'Somei-yoshino' across the Japanese archipelago. J Plant Res, 131:709-717, 2018

 10. Udagawa H, Umemura S, Murakami I, Mimaki S, Makinoshima H, Ishii G, Miyoshi T, Kirita K, Matsumoto S, Yoh K, Niho S, Tsuchihara K, Goto K. Genetic profiling-based prognostic prediction of patients with advanced small-cell lung cancer in large scale analysis. Lung Cancer, 126:182-188, 2018

 11. Sato Y, Matsuda S, Maruyama A, Nakayama J, Miyashita T, Udagawa H, Umemura S, Yanagihara K, Ochiai A, Tomita M, Soga T, Tsuchihara K, Makinoshima H. Metabolic Characterization of Antifolate Responsiveness and Non-responsiveness in Malignant Pleural Mesothelioma Cells. Front Pharmacol, 9:1129, 2018

 12. Fujioka R, Mochizuki N, Ikeda M, Sato A, Nomura S, Owada S, Yomoda S, Tsuchihara K, Kishino S, Esumi H. Change in plasma lactate concentration during arctigenin administration in a phase I clinical trial in patients with gemcitabine-refractory pancreatic cancer. PLoS ONE, 13:e0198219, 2018

 13. Ueda T, Aokage K, Mimaki S, Tane K, Miyoshi T, Sugano M, Kojima M, Fujii S, Kuwata T, Ochiai A, Kusumoto M, Suzuki K, Tsuchihara K, Nishikawa H, Goto K, Tsuboi M, Ishii G. Characterization of the tumor immune-microenvironment of lung adenocarcinoma associated with usual interstitial pneumonia. Lung Cancer, 126:162-169, 2018

 14. Kato M, Nakamura H, Nagai M, Kubo T, Elzawahry A, Totoki Y, Tanabe Y, Furukawa E, Miyamoto J, Sakamoto H, Matsumoto S, Sunami K, Arai Y, Suzuki Y, Yoshida T, Tsuchihara K, Tamura K, Yamamoto N, Ichikawa H, Kohno T, Shibata T. A computational tool to detect DNA alterations tailored to formalin-fixed paraffin- embedded samples in cancer clinical sequencing. Genome Med, 10:44, 2018