Annual Report 2022
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 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 develop the Borderless Gene test, which is based on the technology of the NCC Oncopanel test and whole genome sequencing. This test will go beyond the limitations of the present CGPs, which can only analyze defined sets of genes.
In collaboration with the Division of Genome Biology of the Research Institute, Kyoto University, the University of Tsukuba, and others, we have developed an in silico method 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 method employs molecular dynamics simulation using multiple supercomputers such as FUGAKU and TSUBAME 3.0.
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 2022
Journal
1. Seki Y, Yoshida T, Kohno T, Masuda K, Okuma Y, Goto Y, Horinouchi H, Yamamoto N, Kuwano K, Ohe Y. Liquid biopsy for the detection of resistance mutations to ROS1 and RET inhibitors in non-small lung cancers: A case series study. Respiratory investigation, 60:852-856, 2022
2. Fukuhara S, Oshikawa-Kumade Y, Kogure Y, Shingaki S, Kariyazono H, Kikukawa Y, Koya J, Saito Y, Tabata M, Yoshifuji K, Mizuno K, Miyagi-Maeshima A, Matsushita H, Sugiyama M, Ogawa C, Inamoto Y, Fukuda T, Sugano M, Yamauchi N, Minami Y, Hirata M, Yoshida T, Kohno T, Kohsaka S, Mano H, Shiraishi Y, Ogawa S, Izutsu K, Kataoka K. Feasibility and clinical utility of comprehensive genomic profiling of hematological malignancies. Cancer science, 113:2763-2777, 2022
3. Nagai S, Nishihara H, Suzuki T, Nishio K, Taniguchi H, Tsuchihara K, Nakamura K, Takamatsu R, Ueno T, Aburatani H, Kohno T, Kohsaka S. Recommendations related to the analytical equivalence assessment of gene panel testing. Cancer science, 113:3282-3290, 2022
4. Tabata J, Nakaoku T, Araki M, Yoshino R, Kohsaka S, Otsuka A, Ikegami M, Ui A, Kanno SI, Miyoshi K, Matsumoto S, Sagae Y, Yasui A, Sekijima M, Mano H, Okuno Y, Okamoto A, Kohno T. Novel Calcium-Binding Ablating Mutations Induce Constitutive RET Activity and Drive Tumorigenesis. Cancer research, 82:3751-3762, 2022