Annual Report 2023
Division of Translational Genomics (Tsukiji Campus)
Takashi Kohno
Introduction
This division aims to facilitate cancer precision medicine by implementing next-generation sequencing (NGS)-based tumor profiling systems and advanced annotation of variants.
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 Hospital. Our division developed an NGS-based tumor profiling system, 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 advanced the development of the Borderless Gene Test based on whole-genome sequencing technology. Additionally, we aggregated data from the TOP-GEAR study, which successfully implemented a gene panel test (NCC Oncopanel), demonstrating that comprehensive genome profiling is useful for treatment selection in patients with early lines of treatment or rare cancers (Figure 1).
In collaboration with the Division of Genome Biology of the Research Institute, Kyoto University, the University of Tsukuba, and others, we utilized multiple supercomputers, including 'Fugaku' and 'TSUBAME3.0,' to interpret variants of unknown significance of the RET gene and estimate potential drug sensitivities. The results demonstrate that molecular dynamics simulation enables the in silico interpretation of variants of unknown significance.
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 variants of unknown significance in druggable genes.
List of papers published in 2023
Journal
1. Yoshida T, Yatabe Y, Kato K, Ishii G, Hamada A, Mano H, Sunami K, Yamamoto N, Kohno T. The evolution of cancer genomic medicine in Japan and the role of the National Cancer Center Japan. Cancer Biol Med. 2023 May 3:j.issn.2095-3941.2023.0036.
2. Saito R, Kuroda T, Yoshida H, Sudo K, Saito M, Tanabe H, Takano H, Yamada K, Kiyokawa T, Yonemori K, Kato T, Okamoto A, Kohno T. Genetic characteristics of platinum-sensitive ovarian clear cell carcinoma. Jpn J Clin Oncol. 53(9): 781-790, 2023.
3. Tao K, Yamazaki F, Kubo T, Sunami K, Kumamoto T, Arakawa A, Sugiyama M, Watanabe Y, Nakajima M, Shirakawa N, Tanimura K, Koyama T, Hirata M, Sudo K, Tanabe N, Watanabe T, Yoshida T, Kitami M, Yoshida A, Yatabe Y, Nakano Y, Ohira M, Kamijo T, Nakazawa A, Kato M, Ichimura K, Kohno T, Yamamoto N, Hishiki T, Ichikawa H, Ogawa C. Pediatric Precision Medicine at the National Cancer Center Japan: Prospective Genomic Study of Pediatric Patients with Cancer as Part of the TOP-GEAR Project. JCO Precis Oncol. 2023 Jul;7:e2200266.