IDOGAWA Masashi

写真a

Affiliation

Institute of Cancer Research, Department of Medical Genome Sciences

Job title

Associate Professor

Homepage URL

https://web.sapmed.ac.jp/canmol/

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Education 【 display / non-display 】

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    2002

    Sapporo Medical University  

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    2002

    Sapporo Medical University   医学研究科  

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    1997

    Sapporo Medical University  

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    1997

    Sapporo Medical University   School of Medicine  

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Degree 【 display / non-display 】

  • 札幌医科大学   M.D., Ph.D.

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Professional Memberships 【 display / non-display 】

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    JAPANESE SOCIETY FOR BIOINFORMATICS

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    American Association of Cancer Research

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    American Associtaion for Cancer Research

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    THE JAPAN SOCIETY OF HUMAN GENETICS

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    THE JAPANESE CANCER ASSOCIATION

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Research Areas 【 display / non-display 】

  • Life sciences   Molecular biology  

  • Life sciences   Gastroenterology  

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Affiliation 【 display / non-display 】

  • Sapporo Medical University   Department of Medical Genome Sciences, Institute for Frontier Medicine, Sapporo Medical University School of Medicine.   Associate Professor  

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Research Interests 【 display / non-display 】

  • 癌

  • Cancer

  • 消化器

  • Carcinogenesis

  • 腫瘍

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Papers 【 display / non-display 】

  • Genomic analysis of an aggressive hepatic leiomyosarcoma case following treatment for hepatocellular carcinoma.

    Yuto Numata, Noriyuki Akutsu, Masashi Idogawa, Kohei Wagatsuma, Yasunao Numata, Keisuike Ishigami, Tomoya Nakamura, Takehiro Hirano, Yujiro Kawakami, Yoshiharu Masaki, Ayako Murota, Shigeru Sasaki, Hiroshi Nakase

    Hepatology research : the official journal of the Japan Society of Hepatology    2024.03  [International journal]

    　View Summary

    A 70-year-old man undergoing treatment for immunoglobulin G4-related disease developed a liver mass on computed tomography during routine imaging examination. The tumor was located in the hepatic S1/4 region, was 38 mm in size, and showed arterial enhancement on dynamic contrast-enhanced computed tomography. We performed a liver biopsy and diagnosed moderately differentiated hepatocellular carcinoma. The patient underwent proton beam therapy. The tumor remained unchanged but enlarged after 4 years. The patient was diagnosed with hepatocellular carcinoma recurrence and received hepatic arterial chemoembolization. However, 1 year later, the patient developed jaundice, and the liver tumor grew in size. Unfortunately, the patient passed away. Autopsy revealed that the tumor consisted of spindle-shaped cells exhibiting nuclear atypia and a fission pattern and tested positive for α-smooth muscle actin and vimentin. No hepatocellular carcinoma components were observed, and the patient was pathologically diagnosed with hepatic leiomyosarcoma. Next-generation sequencing revealed somatic mutations in CACNA2D4, CTNNB1, DOCK5, IPO8, MTMR1, PABPC5, SEMA6D, and ZFP36L1. Based on the genetic mutation, sarcomatoid hepatocarcinoma was the most likely pathogenesis in this case. This mutation is indicative of the transition from sarcomatoid hepatocarcinoma to hepatic leiomyosarcoma.

    DOI PubMed

  • The frequency and pathogenicity of BRCA1 and BRCA2 variants in the general Japanese population.

    Masashi Idogawa, Tasuku Mariya, Yumi Tanaka, Tsuyoshi Saito, Hiroshi Nakase, Takashi Tokino, Akihiro Sakurai

    Journal of human genetics    2024.02  [International journal]

    　View Summary

    Hereditary breast and ovarian cancer syndrome (HBOC) resulting from pathogenic variants of BRCA1 or BRCA2 is the most common and well-documented hereditary tumor. Although founder variants have been identified in population-based surveys in various countries, the types of variants are not uniform across races and regions. Recently, the Tohoku Medical Megabank Organization (ToMMo) released whole-genome sequence data including approximately 54,000 individuals from the general population of the Tohoku area in Japan. We analyzed these data and comprehensively identified the prevalence of BRCA1/2 pathogenic and truncating variants. We believe that an accurate understanding of the unique distribution and characteristics of pathogenic BRCA1/2 variants in Japan through this analysis will enable better surveillance and intervention for HBOC patients, not only in Japan but also worldwide.

    DOI PubMed

  • Effects of temozolomide on tumor mutation burden and microsatellite instability in melanoma cells.

    Masahide Sawada, Tokimasa Hida, Takafumi Kamiya, Tomoyuki Minowa, Junji Kato, Masae Okura, Masashi Idogawa, Takashi Tokino, Hisashi Uhara

    The Journal of dermatology    2023.09  [International journal]

    　View Summary

    The efficacy of combination therapy with an immune checkpoint inhibitor (ICI) and cytotoxic chemotherapeutic agents has been investigated in cancer, including melanoma. Before ICIs were introduced, dacarbazine or temozolomide (TMZ) were used to treat melanoma. Several studies using glioma or colorectal cancer cells showed that TMZ can increase the tumor mutation burden (TMB) and induce mismatch repair (MMR) deficiency associated with microsatellite instability (MSI). These could increase immunoreactivity to an ICI, but this has not been evaluated in melanoma cells. We investigated the effects of TMZ on MSI status and TMB in melanoma cells. To evaluate the TMB, we performed whole-exome sequencing using genomic DNA from the human melanoma cell lines Mel18, A375, WM266-4, G361, and TXM18 before and after TMZ treatment. Polymerase chain reaction amplification of five mononucleotide repeat markers, BAT25, BAT26, NR21, NR24, and MONO27, was performed, and we analyzed changes in the MSI status. In all cell lines, the TMB was increased after TMZ treatment (the change amount of TMB with ≤ 5% variant allele frequency [VAF] was 18.0-38.3 mutations per megabase) even in the condition without obvious cytological damage. MSI after TMZ treatment was not observed in any cells. TMZ increased TMB but did not change MSI status in melanoma cells.

    DOI PubMed

  • TM4SF1-AS1 inhibits apoptosis by promoting stress granule formation in cancer cells

    Hiroshi Kitajima, Reo Maruyama, Takeshi Niinuma, Eiichiro Yamamoto, Akira Takasawa, Kumi Takasawa, Kazuya Ishiguro, Akihiro Tsuyada, Ryo Suzuki, Gota Sudo, Toshiyuki Kubo, Kei Mitsuhashi, Masashi Idogawa, Shoichiro Tange, Mutsumi Toyota, Ayano Yoshido, Kohei Kumegawa, Masahiro Kai, Kazuyoshi Yanagihara, Takashi Tokino, Makoto Osanai, Hiroshi Nakase, Hiromu Suzuki

    Cell Death & Disease ( Springer Science and Business Media LLC )  14 ( 7 )  2023.07

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    Abstract Long noncoding RNAs (lncRNAs) play pivotal roles in tumor development. To identify dysregulated lncRNAs in gastric cancer (GC), we analyzed genome-wide trimethylation of histone H3 lysine 4 (H3K4me3) to screen for transcriptionally active lncRNA genes in the non-tumorous gastric mucosa of patients with GC and healthy individuals. We found that H3K4me3 at TM4SF1-AS1 was specifically upregulated in GC patients and that the expression of TM4SF1-AS1 was significantly elevated in primary and cultured GC cells. TM4SF1-AS1 contributes to GC cell growth in vitro and in vivo, and its oncogenic function is mediated, at least in part, through interactions with purine-rich element-binding protein α (Pur-α) and Y-box binding protein 1 (YB-1). TM4SF1-AS1 also activates interferon signaling in GC cells, which is dependent on Pur-α and RIG-I. Chromatin isolation by RNA purification (ChIRP)-mass spectrometry demonstrated that TM4SF1-AS1 was associated with several stress granule (SG)-related proteins, including G3BP2, RACK1, and DDX3. Notably, TM4SF1-AS1 promoted SG formation and inhibited apoptosis in GC cells by sequestering RACK1, an activator of the stress-responsive MAPK pathway, within SGs. TM4SF1-AS1-induced SG formation and apoptosis inhibition are dependent on Pur-α and YB-1. These findings suggested that TM4SF1-AS1 contributes to tumorigenesis by enhancing SG-mediated stress adaptation.

    DOI

  • Junctional adhesion molecule 3 is a potential therapeutic target for small cell lung carcinoma.

    Miki Yamaguchi, Sachie Hirai, Masashi Idogawa, Toshiyuki Sumi, Hiroaki Uchida, Naoki Fujitani, Motoko Takahashi, Yuji Sakuma

    Experimental cell research   426 ( 2 ) 113570 - 113570  2023.05  [International journal]

    　View Summary

    There are few effective therapies for small cell lung carcinoma (SCLC); thus, we need to develop novel and efficacious treatments. We hypothesized that an antibody-drug conjugate (ADC) could be a promising option for SCLC. Several publicly available databases were used to demonstrate the extent to which junctional adhesion molecule 3 (JAM3) mRNA was expressed in SCLC and lung adenocarcinoma cell lines and tissues. Three SCLC cell lines, Lu-135, SBC-5, and Lu-134 A, were selected and examined for JAM3 protein expression by flow cytometry. Finally, we examined the response of the three SCLC cell lines to a conjugate between an anti-JAM3 monoclonal antibody HSL156 (developed in-house) and the recombinant protein DT3C, which consists of diphtheria toxin lacking the receptor-binding domain but containing the C1, C2, and C3 domains of streptococcal protein G. In silico analyses revealed that JAM3 mRNA was expressed higher in SCLC cell lines and tissues than in those of lung adenocarcinoma. As expected, all the three SCLC cell lines examined were positive for JAM3 at the mRNA and protein levels. Consequently, control SCLC cells, but not JAM3-silenced ones, were highly sensitive to HSL156-DT3C conjugates, resulting in dose- and time-dependent decreased viability. Finally, silencing JAM3 alone suppressed the growth of all SCLC cell lines examined. Taken together, these findings suggest that an ADC targeting JAM3 could represent a new approach to treating SCLC patients.

    DOI PubMed

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Misc 【 display / non-display 】

  • Molecular mechanisms of suppression of Claudin-1 expression in oral cancer cell lines

    丹下正一朗, 井戸川雅史, 川島秀器, 佐々木泰史, 時野隆至

    日本分子生物学会年会プログラム・要旨集(Web)   46th  2023

    J-GLOBAL

  • MYO5A-NTRK3融合遺伝子を検出したatypical Spitz tumor

    佐藤 さゆり, 肥田 時征, 井戸川 雅史, 黄倉 真恵, 宇原 久

    日本皮膚科学会雑誌 ( (公社)日本皮膚科学会 )  132 ( 5 ) 1363 - 1363  2022.05

  • Identification of novel prognosticator gene in malignant pancreatic cancer

    Shoichiro Tange, Tomomi Hirano, Masashi Idogawa, Eishu Hirata, Issei Imoto, Takashi Tokino

    CANCER SCIENCE ( WILEY )  113  2022.02

    Research paper, summary (international conference)  

  • 膵臓がんにおける新規予後予測遺伝子の機能解析

    丹下 正一朗, 平野 朋美, 井戸川 雅史, 平田 英周, 井本 逸勢, 時野 隆至

    日本癌学会総会記事 ( (一社)日本癌学会 )  80回   [J15 - 6]  2021.09

  • 長鎖非コードRNA lncAC1は大腸癌の進行を促進する

    小泉 昌代, 井戸川 雅史, 丹下 正一朗, 時野 隆至

    日本癌学会総会記事 ( (一社)日本癌学会 )  80回   [P14 - 5]  2021.09

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Industrial Property Rights 【 display / non-display 】

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Research Projects 【 display / non-display 】

  • Comprehensive analysis of genetic mutations and fusions in Japanese melanoma

    Grant-in-Aid for Scientific Research (C)

    Project Year :

    2021.04
    -
    2024.03
     

    肥田 時征, 井戸川 雅史

  • 非コードRNAの発現ネットワーク解析に基づく消化器癌病態の解明と診断治療への応用

    基盤研究(C)

    Project Year :

    2019.04
    -
    2023.03
     

    井戸川 雅史

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    長鎖非コードRNA（long non-coding RNA, lncRNA）が，癌などの疾患病態においても重要な役割を果たしていることが明らかとなりつつある．そこでまず，The Cancer Genome Atlas （TCGA）の消化器癌RNA-seqデータを用いて，長鎖非コードRNA（lncRNA）を含む遺伝子転写産物の発現量を定量した．このデータを用いて，各消化器癌組織において正常と比較して腫瘍で統計学的に有意に発現が上昇しているlncRNAを抽出した．また各lncRNAについて，生存情報を用いてKaplan-Meier法による解析を行い，低発現群と比べて高発現群で有意に生存率が低下しているlncRNAを同定した．更に，網羅的な遺伝子およびlncRNA発現データを用いたネットワーク解析を行い，正常と比較して，腫瘍で他の遺伝子と発現関連性を多く持つハブlncRNAの同定も試みた．以上の解析から得られた情報を組み合わせて，癌進展に寄与する可能性のある複数のlncRNAの抽出を行った．次に，これらのlncRNAそれぞれに対して2種類のsiRNAの設計を行った，このsiRNAを消化器癌細胞株に導入したところ，lncRNA発現のノックダウンが確認された．この条件下において癌細胞の増殖を定量したところ，複数のlncRNAでそのノックダウンにより有意に増殖の抑制が認められた．更にcaspase-3活性の測定によりアポトーシスを定量したところ，これらのlncRNAのノックダウンによりアポトーシスの増強が認められた．以上の結果から，これらのlncRNAが消化器癌の促進に寄与していることが考えられる．そこで，これらのlncRNAの中で強く増殖抑制やアポトーシス増強が認められたものについて，ノックダウン時の網羅的な遺伝子発現変化をRNAシーケンスを用いて解析を進めているところである．

  • The analysis of non-coding RNA induced by cancer-associtated transcriptional factors in gastrointestinal cancers

    Grant-in-Aid for Scientific Research (C)

    Project Year :

    2016.04
    -
    2020.03
     

    Idogawa Masashi

    　View Summary

    p53 is one of the most important tumor suppressor genes and the direct transcriptional targets of p53 must be explored to elucidate its functional mechanisms. Thus far, the p53 targets that have been primarily studied are protein-coding genes. In this study, analysis of next-generation chromatin immunoprecipitation-sequencing (ChIP-seq) data for p53 revealed that the lncRNA NEAT1 is a direct transcriptional target of p53. The suppression of NEAT1 induction by p53 attenuates the inhibitory effect of p53 on cancer cell growth and also modulates gene transactivation, including that of many lncRNAs. Furthermore, low expression of NEAT1 is related to poor prognosis in several cancers. These results indicate that the induction of NEAT1 expression contributes to the tumor-suppressor function of p53 and suggest that p53 and NEAT1 constitute a transcriptional network contributing to various biological functions and tumor suppression.

  • Platform for Advanced Genome Science

    Grant-in-Aid for Scientific Research on Innovative Areas ― Platforms for Advanced Technologies and Research Resources

    Project Year :

    2016
    -
    2021
     

    KOHARA Yuji, Kato Kazuto, Kawashima Minae, TOYODA Atsushi, Suzuki Yutaka, MITSUI Jun, Hayashi Tetsuya, TOKINO Takashi, Kurokawa Ken, Nakamura Yasukazu, Noguchi Hideki, IWASAKI WATARU, Morishita Shinichi, Asai Kiyoshi, Kasahara Masahiro, Ito Takehiko, Yamada Takuji, KUHARA Satoshi, Takahashi Hiroki, Sakakibara Yasubumi, HAMADA MICHIAKI, Takagi Toshihisa, SESE JUN, Ogura Yoshitoshi, Ida Ryuichi, YAMAGATA Zentaro, Masui Toru, Muto Kaori, Kodama Satoshi, Setoyama Koichi, Kokado Minori, Ohashi Noriko, FUJIYAMA Asao, INOUE Ituro, Nakaoka Hirofumi, Sugano Sumio, Tsuji Shoji, Gotoh Yasuhiro, Nakamura Keiji, Ogura Yoshitoshi, Okuno Miki, Nakase Hiroshi, SASAKI Yasushi, IDOGAWA Masashi, Tange Shoichiro, Mori Hiroshi, OGASAWARA Osamu, Tanizawa Yasuhiro, Kondo Shinji, kiryu hisanori, Kajitani Rei, TASHIRO Kosuke, Frith Martin, HIRAKAWA Hideki, Suzuki Hiromu, NOSHO KATSUHIKO, KAI Masahiro

    　View Summary

    Our group has provided the state of art genome technologies, named PAGS Support, including de novo genome sequencing, variation analysis, epigenomics, RNA analysis, metagenome analysis and single cell analysis, to the projects that were selected from proposals based on KAKENHI projects. Thus far, we have provided PAGS Support to altogether 912 proposals that were selected from 1988 proposals. The proposals cover the most fields of life sciences, expanding to the fields of physical sciences, environmental studies and so on. Thus far 556 papers have been published as the outcome, which covers from biology to agriculture, medicine and pharmacy, from basic to applied sciences. Our group has also developed new technologies and algorithms to overcome the problems emerged in the PAGS Support, which are used in the other PAGS Support projects. This is a positive cycle and therefore our system becomes a very effective way for the promotion of biological sciences.

  • Functional analysis of large intergenic non-coding RNAs regulated by p53 in cancers of digestive organs

    Grant-in-Aid for Scientific Research (C)

    Project Year :

    2013.04
    -
    2017.03
     

    Masashi Idogawa

    　View Summary

    p53 is one of the most important known tumor suppressor genes, and it is inactivated in approximately half of human cancers. To identify the direct transcriptional targets of p53, we performed chromatin immunoprecipitation together with next-generation sequencing (ChIP-seq) and searched for p53 binding motifs across the entire human genome. Among the identified ChIP-seq peaks, approximately half were located in an intergenic region. Therefore, we assumed large intergenic non-coding RNAs (lincRNAs) to be major targets of the p53 family. Through a combination of ChIP-seq and in silico analyses, we found 23 lincRNAs that are upregulated by the p53 family. Additionally, knockdown of specific lincRNAs modulated p53-induced apoptosis and promoted the transcription of a gene cluster. Our results suggest that p53 family members and lincRNAs constitute a complex transcriptional network involved in various biological functions and tumor suppression.

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Presentations 【 display / non-display 】

  • MYO5A-NTRK3融合遺伝子を検出したatypical Spitz tumor

    佐藤 さゆり, 肥田 時征, 井戸川 雅史, 黄倉 真恵, 宇原 久

    日本皮膚科学会雑誌  (公社)日本皮膚科学会

    Presentation date： 2022.05

    Event date：
    2022.05
    　
    　

  • 症例特異的変異を用いた頭頸部扁平上皮癌におけるctDNAモニタリング

    古後 龍之介, 真子 知美, 岩谷 岳, 西塚 哲, 佐々木 泰史, 井戸川 雅史, 時野 隆至, 中川 尚志

    日本癌学会総会記事  (一社)日本癌学会

    Presentation date： 2021.09

    Event date：
    2021.09
    　
    　

  • 膵臓がんにおける新規予後予測遺伝子の機能解析

    丹下 正一朗, 平野 朋美, 井戸川 雅史, 平田 英周, 井本 逸勢, 時野 隆至

    日本癌学会総会記事  (一社)日本癌学会

    Presentation date： 2021.09

    Event date：
    2021.09
    　
    　

  • 長鎖非コードRNA lncAC1は大腸癌の進行を促進する

    小泉 昌代, 井戸川 雅史, 丹下 正一朗, 時野 隆至

    日本癌学会総会記事  (一社)日本癌学会

    Presentation date： 2021.09

    Event date：
    2021.09
    　
    　

  • RAS野生型転移性大腸癌患者における循環腫瘍DNA中のRAS、BRAF、PIK3CA変異の同定と腫瘍組織の変異との比較

    澤田 武, 久保田 英嗣, 中村 慶史, 高橋 直樹, 太田 亮介, 井戸川 雅史, 佐々木 泰史, 時野 隆至, 源 利成, 片岡 洋望

    日本癌学会総会記事  (一社)日本癌学会

    Presentation date： 2021.09

    Event date：
    2021.09
    　
    　

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