Updated on 2024/11/28

Information

 

写真a

 
OTSUJI RYOSUKE
 
Organization
Kyushu University Hospital Neurosurgery Assistant Professor
Title
Assistant Professor

Papers

  • Hemizygous deletion of cyclin-dependent kinase inhibitor 2A/B with p16 immuno-negative and methylthioadenosine phosphorylase retention predicts poor prognosis in IDH-mutant adult glioma Reviewed International journal

    Otsuji, R; Hata, N; Yamamoto, H; Kuga, D; Hatae, R; Sangatsuda, Y; Fujioka, Y; Noguchi, N; Sako, A; Togao, O; Yoshitake, T; Nakamizo, A; Mizoguchi, M; Yoshimoto, K

    NEURO-ONCOLOGY ADVANCES   6 ( 1 )   vdae069   2024.7   eISSN:2632-2498

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Neuro-Oncology Advances  

    Background. Homozygous deletion of the tumor suppression genes cyclin‑dependent kinase inhibitor 2A/B (CDKN2A/B) is a strong adverse prognostic factor in IDH‑mutant gliomas, particularly astrocytoma. However, the impact of hemizygous deletion of CDKN2A/B is unknown. Furthermore, the influence of CDKN2A/B status in IDH‑ mutant and 1p/19q‑codeleted oligodendroglioma remains controversial. We examined the impact of CDKN2A/B status classification, including hemizygous deletions, on the prognosis of IDH‑mutant gliomas. Methods. We enrolled 101 adults with IDH‑mutant glioma between December 2002 and November 2021. CDKN2A/B deletion was evaluated with multiplex ligation‑dependent probe amplification (MLPA). Immunohistochemical anal‑ ysis of p16/MTAP and promoter methylation analysis with methylation‑specific MLPA was performed for cases with CDKN2A/B deletion. Kaplan − Meier plots and Cox proportion hazards model analyses were performed to evaluate the impact on overall (OS) and progression‑free survival. Results. Of 101 cases, 12 and 4 were classified as hemizygous and homozygous deletion, respectively. Immunohistochemistry revealed p16‑negative and MTAP retention in cases with hemizygous deletion, whereas homozygous deletions had p16‑negative and MTAP loss. In astrocytoma, OS was shorter in the order of homozy‑ gous deletion, hemizygous deletion, and copy‑neutral groups (median OS: 38.5, 59.5, and 93.1 months, respec‑ tively). Multivariate analysis revealed hazard ratios of 9.30 (P = .0191) and 2.44 (P = .0943) for homozygous and hemizygous deletions, respectively. Conclusions. CDKN2A/B hemizygous deletions exerted a negative impact on OS in astrocytoma. Immunohistochemistry of p16/MTAP can be utilized to validate hemizygous or homozygous deletions in combina‑ tion with conventional molecular diagnosis.

    DOI: 10.1093/noajnl/vdae069

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  • Supramaximal Resection Can Prolong the Survival of Patients with Cortical Glioblastoma: A Volumetric Study Reviewed International journal

    OTSUJI Ryosuke, HATA Nobuhiro, FUNAKOSHI Yusuke, KUGA Daisuke, TOGAO Osamu, HATAE Ryusuke, SANGATSUDA Yuhei, FUJIOKA Yutaka, TAKIGAWA Kosuke, SAKO Aki, KIKUCHI Kazufumi, YOSHITAKE Tadamasa, YAMAMOTO Hidetaka, MIZOGUCHI Masahiro, YOSHIMOTO Koji

    Neurologia medico-chirurgica   63 ( 8 )   364 - 374   2023.8   ISSN:04708105 eISSN:13498029

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:The Japan Neurosurgical Society  

    <p>We aimed to retrospectively determine the resection rate of fluid-attenuated inversion recovery (FLAIR) lesions to evaluate the clinical effects of supramaximal resection (SMR) on the survival of patients with glioblastoma (GBM). Thirty-three adults with newly diagnosed GBM who underwent gross total tumor resection were enrolled. The tumors were classified into cortical and deep-seated groups according to their contact with the cortical gray matter. Pre- and postoperative FLAIR and gadolinium-enhanced T1-weighted imaging tumor volumes were measured using a three-dimensional imaging volume analyzer, and the resection rate was calculated. To evaluate the association between SMR rate and outcome, we subdivided patients whose tumors were totally resected into the SMR and non-SMR groups by moving the threshold value of SMR in 10% increments from 0% and compared their overall survival (OS) change. An improvement in OS was observed when the threshold value of SMR was 30% or more. In the cortical group (n = 23), SMR (n = 8) tended to prolong OS compared with gross total resection (GTR) (n = 15), with the median OS of 69.6 and 22.1 months, respectively (p = 0.0945). Contrastingly, in the deep-seated group (n = 10), SMR (n = 4) significantly shortened OS compared with GTR (n = 6), with median OS of 10.2 and 27.9 months, respectively (p = 0.0221). SMR could help prolong OS in patients with cortical GBM when 30% or more volume reduction is achieved in FLAIR lesions, although the impact of SMR for deep-seated GBM must be validated in larger cohorts.</p>

    DOI: 10.2176/jns-nmc.2022-0351

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    CiNii Research

  • Liquid biopsy with multiplex ligation-dependent probe amplification targeting cell-free tumor DNA in cerebrospinal fluid from patients with adult diffuse glioma Reviewed International journal

    Otsuji, R; Fujioka, Y; Hata, N; Kuga, D; Sangatsuda, Y; Takigawa, K; Funakoshi, Y; Sako, A; Yamamoto, H; Nakamizo, A; Mizoguchi, M; Yoshimoto, K

    NEURO-ONCOLOGY ADVANCES   5 ( 1 )   vdac178   2023.1   eISSN:2632-2498

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Neuro-Oncology Advances  

    Background: Copy number alterations (CNAs) are common in diffuse gliomas and have been shown to have diagnostic significance. While liquid biopsy for diffuse glioma has been widely investigated, techniques for detecting CNAs are currently limited to methods such as next-generation sequencing. Multiplex ligation-dependent probe amplification (MLPA) is an established method for copy number analysis in pre-specified loci. In this study, we investigated whether CNAs could be detected by MLPA using patients' cerebrospinal fluid (CSF). Methods: Twenty-five cases of adult diffuse glioma with CNAs were selected. Cell-free DNA (cfDNA) was extracted from the CSF, and DNA sizes and concentrations were recorded. Twelve samples, which had appropriate DNA sizes and concentrations, were subsequently used for analysis. Results: MLPA could be successfully performed in all 12 cases, and the detected CNAs were concordant with those detected using tumor tissues. Cases with epidermal growth factor receptor (EGFR) amplification, combination of gain of chromosome 7 and loss of chromosome 10, platelet-derived growth factor receptor alpha amplification, cyclin-dependent kinase 4 amplification, and cyclin-dependent kinase inhibitor 2A (CDKN2A) homozygous deletion were clearly distinguished from those with normal copy numbers. Moreover, EGFR variant III was accurately detected based on CNA. Conclusions: Thus, our results demonstrate that copy number analysis can be successfully performed by MLPA of cfDNA extracted from the CSF of patients with diffuse glioma.

    DOI: 10.1093/noajnl/vdac178

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  • Glutaminolysis is associated with mitochondrial pathway activation and can be therapeutically targeted in glioblastoma.

    Miki K, Yagi M, Hatae R, Otsuji R, Miyazaki T, Goto K, Setoyama D, Fujioka Y, Sangatsuda Y, Kuga D, Higa N, Takajo T, Hajime Y, Akahane T, Tanimoto A, Hanaya R, Kunisaki Y, Uchiumi T, Yoshimoto K

    Cancer & metabolism   12 ( 1 )   35   2024.11   ISSN:2049-3002

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    Language:English  

    DOI: 10.1186/s40170-024-00364-0

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  • All-in-one bimodal DNA and RNA next-generation sequencing panel for integrative diagnosis of glioma

    Higa N., Akahane T., Kirishima M., Yonezawa H., Makino R., Uchida H., Yokoyama S., Takajo T., Otsuji R., Fujioka Y., Sangatsuda Y., Kuga D., Yamahata H., Hata N., Horie N., Kurosaki M., Yamamoto J., Yoshimoto K., Tanimoto A., Hanaya R.

    Pathology, research and practice   263   155598   2024.11   ISSN:0344-0338

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    Language:English   Publisher:Pathology, research and practice  

    Previously, we constructed a DNA-based next-generation sequencing (NGS) panel for an integrated diagnosis of gliomas according to the 2021 World Health Organization classification system. The aim of the current study was to evaluate the feasibility of a modified panel to include fusion gene detection via RNA-based analysis. Using this bimodal DNA/RNA panel, we analyzed 210 cases of gliomas and others to identify fusion genes in addition to gene alterations, including TERT promoter (TERTp) mutation and 1p/19q co-deletion, in formalin-fixed paraffin-embedded tissues. Of the 210 patients, fusion genes were detected in tumors of 35 patients. Eighteen of 112 glioblastomas (GBs) harbored fusion genes, including EGFR and FGFR3 fusions. In IDH-mutant astrocytoma, 6 of 30 cases showed fusion genes such as MET and NTRK2 fusions. Eleven molecular GBs and 20 not-elsewhere-classified cases harbored no gene fusions. Other 11 tumors including ependymoma, pilocytic astrocytoma, diffuse hemispheric glioma, infant-type hemispheric glioma, and solitary fibrous tumors exhibited diagnostic fusion genes. Overall, our results suggest that the all-in-one bimodal DNA/RNA panel is reliable for detecting diagnostic gene alterations in accordance with the latest WHO classification. The integrative pathological and molecular strategy could be valuable in confirmation of diagnosis and selection of treatment options for brain tumors.

    DOI: 10.1016/j.prp.2024.155598

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Presentations

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MISC

  • Liquid Biopsy for Glioma Using Cell-Free DNA in Cerebrospinal Fluid Reviewed International journal

    Otsuji, R; Fujioka, Y; Hata, N; Kuga, D; Hatae, R; Sangatsuda, Y; Nakamizo, A; Mizoguchi, M; Yoshimoto, K

    CANCERS   16 ( 5 )   2024.3   ISSN:2072-6694 eISSN:2072-6694

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    Authorship:Lead author, Corresponding author   Language:English   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)   Publisher:Cancers  

    Glioma is one of the most common primary central nervous system (CNS) tumors, and its molecular diagnosis is crucial. However, surgical resection or biopsy is risky when the tumor is located deep in the brain or brainstem. In such cases, a minimally invasive approach to liquid biopsy is beneficial. Cell-free DNA (cfDNA), which directly reflects tumor-specific genetic changes, has attracted attention as a target for liquid biopsy, and blood-based cfDNA monitoring has been demonstrated for other extra-cranial cancers. However, it is still challenging to fully detect CNS tumors derived from cfDNA in the blood, including gliomas, because of the unique structure of the blood–brain barrier. Alternatively, cerebrospinal fluid (CSF) is an ideal source of cfDNA and is expected to contribute significantly to the liquid biopsy of gliomas. Several successful studies have been conducted to detect tumor-specific genetic alterations in cfDNA from CSF using digital PCR and/or next-generation sequencing. This review summarizes the current status of CSF-based cfDNA-targeted liquid biopsy for gliomas. It highlights how the approaches differ from liquid biopsies of other extra-cranial cancers and discusses the current issues and prospects.

    DOI: 10.3390/cancers16051009

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  • 【Endosome、Lysosome、Exosome-小胞とは?】Exosomeと疾患 脳腫瘍

    尾辻 亮介, 藤岡 寛, 溝口 昌弘

    Clinical Neuroscience   40 ( 7 )   885 - 888   2022.7   ISSN:0289-0585

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    Language:Japanese   Publisher:(株)中外医学社