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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    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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    THE JAPANESE SOCIETY OF INTERNAL MEDICINE

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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, Cancer Reseearch Institute, 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 】

  • The genomic landscape of cutaneous squamous cell carcinoma in Japan

    Junji Kato, Tokimasa Hida, Masashi Idogawa, Takashi Tokino, Hisashi Uhara

    The Journal of Dermatology    2024.12

    DOI

  • Genetic Characteristics of Cutaneous, Acral, and Mucosal Melanoma in Japan

    Tokimasa Hida, Masashi Idogawa, Junji Kato, Yukiko Kiniwa, Kohei Horimoto, Sayuri Sato, Masahide Sawada, Shoichiro Tange, Masae Okura, Ryuhei Okuyama, Takashi Tokino, Hisashi Uhara

    Cancer Medicine    2024.11

    DOI

  • A case of familial progressive hyperpigmentation with or without hypopigmentation presenting with hypopigmented striae along the lines of Blaschko.

    Tokimasa Hida, Masashi Idogawa, Aki Ishikawa, Masae Okura, Satoru Sasaki, Takashi Tokino, Hisashi Uhara

    The Journal of dermatology    2024.09  [Refereed]  [International journal]

    　View Summary

    Familial progressive hyperpigmentation with or without hypopigmentation (FPHH) is an autosomal dominant disorder characterized by widespread skin hyperpigmentation, café-au-lait spots, and hypopigmented circular macules, resulting from KITLG variants. KITLG, expressed by keratinocytes, binds to KIT on melanocytes, stimulating melanogenesis. Disturbances in the KITLG-KIT interaction result in diffuse hyperpigmentation in FPHH. However, the mechanisms behind hypopigmented macule formation remain unclear. This report presents a unique FPHH case in a patient with a novel KITLG mutation (Ser78Leu). Notably, the patient showed multiple hypopigmented macules and striae along the lines of Blaschko. Digital polymerase chain reaction analysis of the DNA from skin and blood tissues indicated a copy-neutral loss of heterozygosity at the KITLG locus, only in the hypopigmented macule. These findings suggest that the hypopigmented macules might result from revertant mosaicism. Conversely, café-au-lait spots do not follow the lines of Blaschko and can superimpose on the hypopigmented striae, indicating a distinct pathogenesis. This case contributes to the understanding of the genetic mechanisms in FPHH.

    DOI PubMed

  • Genomic landscape of cutaneous, acral, mucosal, and uveal melanoma in Japan: analysis of clinical comprehensive genomic profiling data.

    Tokimasa Hida, Junji Kato, Masashi Idogawa, Takashi Tokino, Hisashi Uhara

    International journal of clinical oncology    2024.09  [Refereed]  [Domestic journal]

    　View Summary

    BACKGROUND: Cutaneous melanoma (CM) is the most common type in Caucasians, while acral melanoma (AM) and mucosal melanoma (MM), which are resistant to immunotherapies and BRAF/MEK-targeted therapies, are more common in East Asians. Genomic profiling is essential for treating melanomas, but such data are lacking in Japan. METHODS: Comprehensive genomic profiling data compiled in the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) were analyzed. RESULTS: A total of 380 melanomas was analyzed, including 136 CM, 46 AM, 168 MM, and 30 uveal melanoma (UM). MM included conjunctival, sinonasal, oral, esophageal, anorectal, and vulvovaginal melanomas. No significant difference in the median tumor mutational burden (TMB) of CM (3.39 mutations/megabase), AM (2.76), and MM (3.78) was the key finding. Microsatellite instability-high status was found in one case. BRAF V600E/K was found in only 45 patients (12%). Key driver mutations in CM were BRAF (38%), NRAS (21%), NF1 (8%), and KIT (10%), with frequent copy number alterations (CNAs) of CDKN2A, CDKN2B, and MYC. AM was characterized by altered KIT (30%), NRAS (26%), and NF1 (11%) and CDKN2A, CDKN2B, CDK4, MDM2, and CCND1 CNAs. MM was characterized by altered NRAS (24%), KIT (21%), and NF1 (17%) and MYC, KIT, and CDKN2A CNAs, with differences based on anatomical locations. UM bore GNAQ or GNA11 driver mutations (87%) and frequent mutations in SF3B1 or BAP1. CONCLUSION: The distinct genomic profiling in Japanese patients, including lower TMB, compared to Caucasians, is associated with poorer treatment outcomes. This result underscores the need for more effective therapeutic agents.

    DOI PubMed

  • Mosaic SUFU mutation associated with a mild phenotype of multiple hereditary infundibulocystic basal cell carcinoma syndrome.

    Marina Hamada, Tokimasa Hida, Masashi Idogawa, Shoichiro Tange, Takafumi Kamiya, Masae Okura, Toshiharu Yamashita, Takashi Tokino, Hisashi Uhara

    The Journal of dermatology    2024.08  [Refereed]  [International journal]

    　View Summary

    Multiple hereditary infundibulocystic basal cell carcinoma syndrome (MHIBCC), an autosomal dominant disorder caused by variants in SUFU, is characterized by numerous infundibulocystic basal cell carcinomas (IBCCs). In this report, we present a possible case of mosaic MHIBCC. A 57-year-old woman underwent the removal of four papules on her face, which were diagnosed as IBCCs. Exome sequencing revealed a SUFU c.1022+1G>A mutation within the skin tumor. The same mutation was detected in her blood but at a lower allele frequency. TA cloning revealed that the allele frequency of the mutation in the blood was 0.07. Additionally, tumor assessment revealed loss of heterozygosity (LOH) in chromosome 10, including the SUFU locus. These results indicate the patient had mosaicism for the SUFU mutation in normal tissues, aligning with the mosaic MHIBCC diagnosis. This, combined with LOH, likely contributed to IBCC development. Mosaic MHIBCC may present with milder symptoms. However, it may still increase the risk of developing brain tumors and more aggressive basal cell carcinoma. The possibility of mosaicism should be investigated in mild MHIBCC cases, where standard genetic tests fail to detect SUFU germline variants.

    DOI PubMed

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Misc 【 display / non-display 】

  • クローズアップ実験法(series 370) 知っていますか?TCGAの更新状況

    丹下 正一朗, 井戸川 雅史, 時野 隆至

    実験医学 ( (株)羊土社 )  42 ( 9 ) 1414 - 1424  2024.06

  • 【メラノーマ診療Up-To-Date】メラノーマの治療選択における包括的がんゲノムプロファイリング検査

    肥田 時征, 加藤 潤史, 井戸川 雅史, 宇原 久

    皮膚病診療 ( (株)協和企画 )  46 ( 1 ) 28 - 33  2024.01

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    ＜文献概要＞ポイント ●包括的がんゲノムプロファイリング(comprehensive genome profiling:CGP,別名:がん遺伝子パネル)検査は,標準治療の終了した(または終了見込みの)固形癌患者が保険診療で受けることができ,現在5種類から選択できる.●CGP検査のエキスパートパネルで非承認薬や適応外薬が推奨された場合,その薬を使用するためには治験,先進医療,臨床研究などに参加する必要がある.●メラノーマでは,BRAFのまれな変異,融合遺伝子,KIT変異などが治療標的として検出される可能性がある.

  • Prospective observational study of monitoring gene alterations in plasma cell-free DNA using droplet digital PCR system during anti-EGFR antibody treatment in patients with RAS wild-type advanced colorectal cancer.

    Naoki Takahashi, Keishi Nakamura, Yosuke Kito, Eiji Kubota, Masako Asayama, Yosuke Kumekawa, Hiroki Hara, Tomohiro Matsushima, Kunihiro Tsuji, Hiromi Kataoka, Akihiro Tsuyada, Yasushi Sasaki, Masashi Idogawa, Takashi Tokino, Takeshi Sawada

    Journal of Clinical Oncology ( American Society of Clinical Oncology (ASCO) )  41 ( 4_suppl ) 172 - 172  2023.02

    Research paper, summary (international conference)  

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    172 Background: Anti-EGFR antibody is recommended as one of the standard treatments in patients with RAS wild-type advanced colorectal cancer (CRC). Few reports have evaluated low-frequency subclones of alterations in EGFR signaling pathway genes in plasma cell-free DNA (cfDNA) during anti-EGFR treatment in prospective cohort of advanced CRC patients. Methods: Key inclusion criteria of this study was as follows: 20 years old and over, performance status 0 to 2, metastatic or recurrent CRC (adenocarcinoma), RAS wild-type CRC diagnosed by PCR-rSSO using tumor tissue, no prior use of anti-EGFR antibody. Plasma samples were prospectively collected at pre-treatment, at 4, 10 weeks, every 10 weeks thereafter, and at the end of the anti-EGFR treatment. With QX200 Droplet Digital PCR platform, we analyzed hotspot mutations of KRAS, NRAS, BRAF, and PIK3CA and copy number (CN) variant of HER2 and MET using plasma samples of pre- and post-treatment as well as during treatment (limited to patients with any gene alterations at pre- and post-treatment). Results: Total 50 patients were registered in this study, but 3 patients were excluded because inclusion criteria were not met. Finally, 47 patients were included in full analysis set. In 15 patients (31.9%), genetic alterations including KRAS (G12G13: 10.1%, A59Q61: 2.2%), NRAS (G12G13: 2.2%, Q61: 2.1%), BRAF (V600: 6.4%) , PIK3CA (E545: 4.3%, H1047: 4.3%) , and HER2 (amplification: 6.5%) were detected in pre-treatment samples. Analysis of pre-treatment samples showed that response rates of patients with any gene alterations (N = 13) and that without any gene alterations (N = 29) were 30.8% and 58.6%, respectively (p = 0.095). When the cut-off of variant allele frequency (VAF) was set as 0.5% in patients with any gene mutations, the response rates for cases with VAF ≥0.5% (N = 6) and those with VAF < 0.5% (N = 7) were 0% and 57.1%, respectively (p = 0.049). Among 41 patients with detectable target lesions by CT scan, there was significant difference in percentage of best tumor shrinkage between patients with gene alterations and those without gene alterations (32.1% vs 10.5%, p = 0.037), when cut-off VAF of any gene mutations was set as 0.5% and cut-off CN of HER2 or MET was set as 4 at pre-treatment. Due to dynamics of each gene alteration in cfDNA during treatment, mutations of KRAS A59Q61, NRAS Q61, and MET amplification were characterized as acquired alterations which were newly detected after the administration of anti-EGFR antibodies. Conclusions: Our study demonstrated the clinical relevance of minor mutant subclones in EGFR signaling pathway genes in plasma for predicting response to anti-EGFR treatment. Although sample size of this study was small, preferable threshold for distinguishing responders from non-responders may be 0.5% as VAF of these gene mutations. Clinical trial information: 000034923 .

    DOI

  • 【新型コロナウイルス感染症パンデミックと医療機器を考える】疫学データから考えるCOVID-19対策の指針

    園生 雅弘, 林 秀行, 下畑 享良, 神林 隆道, 井戸川 雅史

    医療機器学 ( (一社)日本医療機器学会 )  92 ( 3 ) 322 - 330  2022.06

    Authorship：   Last author

  • 【COVID-19-脳神経内科医が診るための最新知識】疫学データから考えるCOVID-19対策の指針

    園生 雅弘, 井戸川 雅史, 神林 隆道, 下畑 享良, 小林 正人, 林 秀行

    BRAIN and NERVE: 神経研究の進歩 ( (株)医学書院 )  72 ( 10 ) 1023 - 1030  2020.10

    　View Summary

    ＜文献概要＞日本は新型コロナウイルス感染症(COVID-19)のPCR検査率が低いことが批判されているが,PCR検査率は封じ込め成功にも死亡率抑制にも関係はなく,封じ込め成功の主因はソーシャル・ディスタンシングと考えられる。日本を含む東アジアの死亡率の低さは感染が広がっていないことも一因である。日本は世界一の高齢化の中,高齢者選択性の極めて高いCOVID-19の死者の抑制に成功している。今後の方策として弱毒化も期待され,日本では東京が先行して軽症化している可能性がある。

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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

    　View Summary

    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 】

  • 長鎖非コードRNA IncAC1はp53標的遺伝子の発現変化を介して大腸癌進展に寄与する(Long non-coding RNA IncAC1 contributes to colorectal cancer progression via the expression change of p53-targeting genes)

    井戸川 雅史, 小泉 昌代, 丹下 正一朗, 平野 朋美, 大久保 陽介, 時野 隆至

    日本癌学会総会記事  (一社)日本癌学会

    Presentation date： 2023.09

    Event date：
    2023.09
    　
    　

  • 再発転移頭頸部癌におけるctDNAモニタリングによる治療効果予測(Prediction of treatment response by ctDNA monitoring in recurrent metastatic head and neck cancer)

    古後 龍之介, 真子 知美, 開 勇人, 西塚 哲, 丹下 正一朗, 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： 2023.09

    Event date：
    2023.09
    　
    　

  • 予後不良の腫瘍と発現が相関する霊長類特異的遺伝子の解析(Analysis of primate-specific genes contributes to malignant cancer)

    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： 2023.09

    Event date：
    2023.09
    　
    　

  • がん遺伝子パネル検査解析支援ソフトウェア「Varporter」の開発と応用

    井戸川 雅史, 田中 佑弥, 櫻井 晃洋, 時野 隆至

    日本遺伝カウンセリング学会誌  (一社)日本遺伝カウンセリング学会

    Presentation date： 2023.06

    Event date：
    2023.06
    　
    　

  • メラノーマ細胞におけるtumor mutation burden及びmicrosatellite instabilityに対するtemozolomideの影響

    澤田 匡秀, 肥田 時征, 神谷 崇文, 箕輪 智幸, 加藤 潤史, 黄倉 真恵, 井戸川 雅史, 時野 隆至, 宇原 久

    日本皮膚悪性腫瘍学会学術大会プログラム・抄録集  (一社)日本皮膚悪性腫瘍学会

    Presentation date： 2023.06

    Event date：
    2023.06
    　
    　

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