Annual Report 2024
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 genetic tests using whole-genome sequencing technology. In addition, by re-analyzing NCC Oncopanel results, we demonstrated the utility of incorporating non-coding regions to preserve the accuracy of TMB (tumor mutational burden) estimates in small-sized panels.
In collaboration with the Division of Genome Biology of the Research Institute, Kyoto University, and others, we utilized supercomputers to interpret RET variants conferring resistance to RET kinase inhibitors. The results demonstrated that molecular dynamics simulation enables the in silico interpretation of variants conferring drug resistance.
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 2024
Journal
1. Arakawa A, Tao K, Kohno T, Ogawa C. Cross-individual cancer transmission to children during the gestational and perinatal periods. Cancer science, 115:1039-1047, 2024
2. Kubo T, Sunami K, Koyama T, Kitami M, Fujiwara Y, Kondo S, Yonemori K, Noguchi E, Morizane C, Goto Y, Maejima A, Iwasa S, Hamaguchi T, Kawai A, Namikawa K, Arakawa A, Sugiyama M, Ohno M, Yoshida T, Hiraoka N, Yoshida A, Yoshida M, Nishino T, Furukawa E, Narushima D, Nagai M, Kato M, Ichikawa H, Fujiwara Y, Kohno T, Yamamoto N. The impact of rare cancer and early-line treatments on the benefit of comprehensive genome profiling-based precision oncology. ESMO open, 9:102981, 2024
3. Nishino T, Yumura M, Sunami K, Kubo T, Ichikawa H, Yasuda T, Furukawa E, Nagai M, Yatabe Y, Kato M, Kohno T. Leveraging non-coding regions to guarantee the accuracy of small-sized panel-based tumor mutational burden estimates. Cancer science, 115:4045-4053, 2024