Annual Report 2023
Division of Brain Tumor Translational Research
Hiromichi Suzuki, Chisato Takahashi, Morita Yoko, Takuma Nakashima, Yuki Yomoda, Yuriko Sugihara, Mai Kitahara, Ryo Yamamoto
Introduction
Malignant brain tumors are highly lethal and aggressive. Despite recent advances in the current therapies including the combination of surgical resection, chemotherapy, and radiotherapy, the prognosis remains poor. Therefore, novel molecular therapies with reduced side effects are highly needed. The recent development of sequencing technology enables us to reveal how malignant tumors form and why some of the tumors are refractory to current therapies. We use genetic tools to reveal brain tumor pathogenesis to lead to the development of novel therapies.
The Team and What We Do
Our team’s expertise is in bioinformatics analysis. We are working on sequencing analysis to reveal the detailed mechanisms of brain tumor pathogenesis and discover novel therapeutic targets. Using human tissues resected in surgical resection, cell lines, and mouse models, we are performing multi-omics analyses including genomic, epigenomic, transcriptomic, and post-transcriptomic data. In addition to that basic research, we are working on clinical applications that enable highly accurate and low-cost diagnosis of brain tumors based on molecular classification.
We provide bioinformatics analyses for other cancer genome projects, especially for urological cancers and retinoblastomas.
Research Activities
1. Multi-omics analyses of brain tumors
Recent advances in sequencing technology enable us to classify brain tumors based on their molecular features leading to precision medicine. Thus far, we have revealed the mutational landscape of glioma and medulloblastoma. Those findings are now used in the WHO classification (Suzuki, H. Nat Genet, 2015). We have joined the national sequencing project as a team for the rare cancers for which our lab is conducting multi-omics analysis of brain tumors. In this project, our lab performed multi-omics sequencing for more than 470 cases with brain tumors and is analyzing the sequencing data to discover novel targets using the world’s largest sequencing data from brain tumors. We are also developing long-read sequencing analysis for brain tumors.
2. Genetic analysis of medulloblastoma
We demonstrated the close relationship between genetic abnormalities and normal brain development of which failure leads to medulloblastoma tumorigenesis. We reported that mutations in the CBFA complex inhibit the normal differentiation of neuronal precursor cells, leading to cellular retention and serving as the origin of medulloblastoma development.
3. Analysis of intratumoral heterogeneity in gliomas
Intratumoral heterogeneity contributes to therapy resistance and tumor progression. We are developing single-cell multi-omics methods and analyses for gliomas to reveal intratumoral heterogeneity in gliomas. We are generating high-quality multi-omics single-cell data in collaboration with the Department of Neurosurgery and Neuro-Oncology. Combining publicly available datasets of single-cell sequencing, we are describing evolutional trajectories associated with brain development and seeking transcriptional vulnerability under the tumor progression.
4. Understanding Genome and Epigenome Aberrations in Upper Tract Urothelial Carcinoma
We are progressing with the comprehensive analysis of open chromatin regions using ATAC-seq and the integration of genomic abnormalities.
Education
We have trained a post-doctoral researcher and two Ph.D. students.
Future Prospects
The development of sequencing technology enables us to analyze what happens in the cancer cell from the perspective of multi-omics. We are using state-of-art technology to uncover how cancer arises and evolves. As we are generating and collecting the world’s largest sequencing data for brain tumors, we are working on bioinformatic analyses which will discover novel therapeutic targets underlying brain tumor pathogenesis. We have also developed rapid clinical applications to diagnose brain tumors, which will lead to the better stratification of patients based on molecular features.
List of papers published in 2023
Journal
1. Nakashima T, Yamamoto R, Ohno M, Sugino H, Takahashi M, Funakoshi Y, Nambu S, Uneda A, Yanagisawa S, Uzuka T, Arakawa Y, Hanaya R, Ishida J, Yoshimoto K, Saito R, Narita Y, Suzuki H. Development of a rapid and comprehensive genomic profiling test supporting diagnosis and research for gliomas. Brain tumor pathology, 41:50-60, 2024
2. Shiba Y, Motomura K, Taniguchi R, Kurimoto M, Mizutani K, Ohka F, Aoki K, Ito E, Nishikawa T, Yamaguchi J, Kibe Y, Shimizu H, Maeda S, Nakashima T, Suzuki H, Muramatsu H, Takahashi Y, Saito R. Efficacy and safety of bevacizumab, irinotecan, and temozolomide combination for relapsed or refractory pediatric central nervous system embryonal tumor: a single-institution study. Journal of neurosurgery. Pediatrics, 1-9, 2023
3. Nishikawa T, Ohka F, Aoki K, Suzuki H, Motomura K, Yamaguchi J, Maeda S, Kibe Y, Shimizu H, Natsume A, Innan H, Saito R. Easy-to-use machine learning system for the prediction of IDH mutation and 1p/19q codeletion using MRI images of adult-type diffuse gliomas. Brain tumor pathology, 40:85-92, 2023