Annual Report 2021
Division of Translational Genomics (Tsukiji Campus)
Takashi Kohno, Hitoshi Ichikawa
Introduction
This division aims to facilitate cancer precision medicine by implementing next-generation sequencing (NGS)-based tumor profiling systems.
The Team and What We Do
This division organizes a clinical sequencing team with staff members from the Department of Experimental Therapeutics, Department of Laboratory Medicine and others in the National Cancer Center Hospitals. Our division aims to implement NGS-based tumor profiling systems, such as NCC Oncopanel, which is now implemented as a comprehensive genome profiling panel (CGP) in Japan.
Research activities
In collaboration with the Department of Bioinformatics of the Research Institute, the Department of Experimental Therapeutics, and the Department of Laboratory Medicine, we are developing the Borderless Gene test. This test is based on the technology of the NCC Oncopanel test, which we developed and is currently used as a CGP test covered by national insurance. This goes beyond the limitations of the present CGPs, which can only analyze defined sets of genes (Figure).
In collaboration with the Division of Genome Biology of the Research Institute, Kyoto University, the University of Tsukuba, and others, we have begun to develop in silico methods for the interpretation of variants of unknown significance (VUSs), which are often found in cancer genome medicine, and for the estimation of drug efficacy. The research aims to establish a clinically feasible method by performing molecular dynamics simulations using multiple supercomputers such as FUGAKU and TSUBAME 3.0, and by integrating the results with biochemical and biological experimental results.
Clinical trials
TOP-GEAR: Trial of Onco-Panel for Gene-profiling to Estimate both Adverse events and Response by Cancer Treatment (UMIN000011141)
Education
Post-doctoral fellows and chief residents in NCC have undergone on-the-job training in several translational research projects.
Future Prospects
Tumor-profiling gene panel tests underpin cancer genome medicine in Japan. However, there is still a gap between the number of patients with actionable mutations and those receiving genomically matched therapy. This gap is largely attributable to the lack of availability of/accessibility to relevant trials and drugs. To fill it, we are collaborating with oncologists for the following two purposes: 1) To facilitate molecularly driven clinical trials by implementing tumor genome profiling tests and 2) To annotate VUSs (variants of unknown significance) in druggable genes.
List of papers published in 2021
Journal
1. Mizuno T, Yoshida T, Sunami K, Koyama T, Okita N, Kubo T, Sudo K, Shimoi T, Ueno H, Saito E, Katanoda K, Shibata T, Yonemori K, Okusaka T, Boku N, Ohe Y, Hiroshima Y, Ueno M, Kuboki Y, Doi T, Nakamura K, Kohno T, Yatabe Y, Yamamoto N. Study protocol for NCCH1908 (UPFRONT-trial): a prospective clinical trial to evaluate the feasibility and utility of comprehensive genomic profiling prior to the initial systemic treatment in advanced solid tumour patients. Japanese journal of clinical oncology, 51:1757-1760, 2021
2. Ishioka K, Yasuda H, Hamamoto J, Terai H, Emoto K, Kim TJ, Hirose S, Kamatani T, Mimaki S, Arai D, Ohgino K, Tani T, Masuzawa K, Manabe T, Shinozaki T, Mitsuishi A, Ebisudani T, Fukushima T, Ozaki M, Ikemura S, Kawada I, Naoki K, Nakamura M, Ohtsuka T, Asamura H, Tsuchihara K, Hayashi Y, Hegab AE, Kobayashi SS, Kohno T, Watanabe H, Ornitz DM, Betsuyaku T, Soejima K, Fukunaga K. Upregulation of FGF9 in Lung Adenocarcinoma Transdifferentiation to Small Cell Lung Cancer. Cancer research, 81:3916-3929, 2021
3. Takeyasu Y, Okuma HS, Kojima Y, Nishikawa T, Tanioka M, Sudo K, Shimoi T, Noguchi E, Arakawa A, Mori T, Sunami K, Kubo T, Kohno T, Akihiko Y, Yamamoto N, Yonemori K. Impact of ALK Inhibitors in Patients With ALK-Rearranged Nonlung Solid Tumors. JCO precision oncology, 5:2021
4. Yoh K, Seto T, Satouchi M, Nishio M, Yamamoto N, Murakami H, Nogami N, Nosaki K, Kohno T, Tsuta K, Nomura S, Ikeno T, Wakabayashi M, Sato A, Matsumoto S, Goto K. Final survival results for the LURET phase II study of vandetanib in previously treated patients with RET-rearranged advanced non-small cell lung cancer. Lung cancer (Amsterdam, Netherlands), 155:40-45, 2021
5. Naito Y, Aburatani H, Amano T, Baba E, Furukawa T, Hayashida T, Hiyama E, Ikeda S, Kanai M, Kato M, Kinoshita I, Kiyota N, Kohno T, Kohsaka S, Komine K, Matsumura I, Miura Y, Nakamura Y, Natsume A, Nishio K, Oda K, Oda N, Okita N, Oseto K, Sunami K, Takahashi H, Takeda M, Tashiro S, Toyooka S, Ueno H, Yachida S, Yoshino T, Tsuchihara K. Clinical practice guidance for next-generation sequencing in cancer diagnosis and treatment (edition 2.1). International journal of clinical oncology, 26:233-283, 2021