共同企画

共同企画教育講演分子と病理形態から解読する脳腫瘍の実像

7月6日（木）　9:00-11:00　Room B 1EL①-1 脳腫瘍の発達と特性獲得に結び付く分子メカニズムと新たな治療戦略の可能性 Molecular mechanisms linking to development and properties of gliomas, and the possibility of new therapeutic strategy. 齋藤　敦, 今泉　和則広大　医　分子細胞 Atsushi Saito, Kazunori Imaizumi Dept. Biochem., Inst. Biomed. Health. Sci., Hiroshima Univ. Brain tumor is an intractable disease for which effective therapeutic strategies have not been established. One of the causes are the diverse types and categories of brain tumors. In addition to the classification into four grades, the subtypes are divided into more than twenty patterns depending on various factors including its origin. The first choice of the treatments is also different among each subtype. Of these brain tumors, glioma is a typical malignant brain tumor with a life expectancy of only fourteen months after definitive diagnosis. So far, the important molecules that are related to its development and categorization have been discovered. Such molecules include not only cell cycle and cell proliferation regulators found in the other tumors, but also various molecules for epigenetic machineries such as DNA methylation. Some of them contribute to the latest categorization of glioma. However, further studies for summarizing many molecules involved in each type of glioma are necessary to understand the link of them with its onset and characteristics. In this talk, I will introduce molecular mechanisms for the development of gliomas and the acquisition of its characteristics. Additionally, I will touch on the latest findings novel molecules involved in glioma development and the prospective possibilities for therapeutic strategies targeting them.		7月6日（木）　9:00-11:00　Room B 1EL①-2 マルチオミクス解析によるグリオーマの病態解明 Multi-omics analysis for malignant gliomas 鈴木　啓道国立がん研究センター　研究所　脳腫瘍連携研究分野 Hiromichi Suzuki Division of Brain Tumor Translational Research, National Cancer Center Research Institute Gliomas are the most common malignant brain tumors. Large-scale sequence studies lead to better molecular classification. Recently, multi-omics analysis is becoming more common, which enables us to investigate glioma cells multi-dimensionally. Japanese whole-genome sequencing (WGS) project launched in August 2021 for precision medicine and research and sequenced more than 10,000 cancer genomes. As part of the project, we have performed deep WGS of about 350 cases with adult gliomas along with multi-omics data including expression and DNA methylation profile. The analysis of mutation and structural variants (SVs) detected previously known driver alterations where some of the drivers have a distinct prevalence among races. While SVs in IDH-mutant gliomas consist of simple SVs, most glioblastomas harbor complex SVs. Deep WGS enables us to delineate a fine view of clonal architecture demonstrating that distinct signatures of mutations and SVs are enriched depending on their developmental stage. Gene expression profiling reveals specific immune cell signatures related to prognosis. Here, we provide the multi-omics overview of adult gliomas, which will lead to a better understanding of glioma pathogenesis. The WGS project is now expanding and is involving further sequencing technologies including long-read sequencing, ATAC-seq, and whole-genome bisulfate sequencing.

7月6日（木）　9:00-11:00　Room B 1EL①-3 グリオーマ患者におけるカスタム遺伝子パネルを用いた組織のtarget sequencingと髄液を用いたliquid biopsy Target sequencing for molecular diagnosis by custom-made NGS panel and liquid biopsy from CSF in glioma patients 吉本　幸司¹, 比嘉　那優大², 藤岡　寛¹, 尾辻　亮介¹, 赤羽　俊章³, 空閑　太亮¹, 花谷　亮典², 谷本　昭英³ 1. 九州大学大学院医学研究院　脳神経外科, 2. 鹿児島大学大学院医歯学総合研究科　脳神経外科, 3. 鹿児島大学大学院医歯学総合研究科　病理学分野 Koji Yoshimoto¹, Nayuta Higa², Yutaka Fujioka¹, Ryosuke Otsuji¹, Toshiaki Akahane³, Daisuke Kuga¹, Hanaya Ryosuke², Akihide Tanimoto³ 1. Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan, 2. Department of Neurosurgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan, 3. Department of Pathology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan After the introduction of molecular integrated diagnosis by the WHO classification scheme in the diagnosis of glioma, the clinically relevant molecular diagnostic methodology is necessary. We analyzed 303 diffuse glioma patients by the recently developed glioma-tailored 50-gene NGS panel. Within glioblastomas (GBM), the most commonly mutated genes were TERTp, TP53, PTEN, NF1, and PDGFRA, which was the most frequently mutated tyrosine kinase receptor in GBM, followed by EGFR. The genes that most commonly showed evidence of loss were PTEN, CDKN2A/B, and RB1, while the genes that most commonly showed evidence of gain/amplification were EGFR, PDGFRA, and CDK4. In 22 grade III origodendroglial tumors, three patients (14%) had CDKN2A/B homozygous deletion, and four patients (18%) had ARID1A mutation. Reclassification based on the WHO 2021 classification resulted in 62.5% of grade II/III IDH wild-type astrocytomas being classified as IDH wild-type GBM and 37.5% as not elsewhere classified. In summary, we successfully reclassified the 303 diffuse glioma cases based on the WHO 2021 classification and clarified the genetic profile of diffuse gliomas in the Japanese population. Lastly, we present our resent data about liquid biopsy, a less invasive diagnostic method, for the molecular diagnosis of high-grade glioma from CSF.		7月6日（木）　9:00-11:00　Room B 1EL①-4 WHO脳腫瘍分類第５版 The fifth edition of the WHO Classification of Tumors of the Central Nervous System 小森　隆司都立神経病院　検査科　神経病理 Takashi Komori Dept. of Lab. Med. & Pathol., Tokyo Metro. Neurol. Hospt. The fifth edition of the WHO Classification of Tumors of the Central Nervous System (WHO CNS5) was published in 2021, introducing significant changes that advance the role of molecular diagnostics in CNS tumor classification. WHO CNS5 established different approaches to tumor nomenclature and grading, and new tumor types and subtypes were introduced, some based on DNA methylation profiling. One of the significant changes was the grading of gliomas, molecular markers obtaining more clinically relevant information that will improve the risk stratification of gliomas. Typical examples include the CDKN2A/B homozygous deletion for IDH-mutant astrocytoma. In addition, for IDH-wildtype astrocytoma, the concurrent gain of whole chromosome 7 and loss of whole chromosome 10, TERT promoter mutations, and EGFR amplification were identified as independent molecular markers of the worst clinical outcomes. Therefore, WHO CNS5 adopted these molecular markers into the revised grading criteria of IDH-mutant and -wildtype astrocytoma as a grading system within tumor types. In addition, molecular alteration-based classification was adopted for diffuse gliomas in children, dividing low-grade and high-grade subcategories. However, an integrated diagnosis combining clinical, histological, and molecular information remains essential to achieving this novel classification feasible in clinical practice.