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Analysis of interregional differences in somatic genetic landscape and prognosis in glioblastoma

Research Project

Project/Area Number 17K16646
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Neurosurgery
Research InstitutionOsaka University (2017, 2019)
Kobe University (2018)

Principal Investigator

Umehara Toru  大阪大学, 医学部附属病院, 医員 (20792469)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords神経膠腫 / 遺伝子変異 / コピー数異常 / 不均一性 / 遺伝子 / クローン進化 / 脳腫瘍 / サンプリング
Outline of Final Research Achievements

We conducted the largest-ever retrospective cohort study for Japanese patients with glioblastoma and investigated the prognostic impact of copy number alterations (CNAs) using two population-based cohorts: an original Japanese cohort and a dataset from The Cancer Genome Atlas (TCGA). The results showed that the triple overlap CNAs in EGFR, CDKN2A, and PTEN (triple CNA) can be a common poor prognostic factor and that the discrepancies in the distribution of triple CNA in these two cohorts could provide a full account of the cohort disparities of survival duration.

Academic Significance and Societal Importance of the Research Achievements

希少疾患である膠芽腫において、国内200例を超えるIDH野生型膠芽腫の分子遺伝学的検討と詳細な生存解析を行った本研究は、アジア発の膠芽腫コホートとしては過去最大級となる。本研究成果により、「Triple CNA」などのゲノムコピー数異常が膠芽腫患者の新たな予後層別化因子となることが明らかとなった。さらにゲノムコピー数異常は、これまで報告されている膠芽腫の地域間予後格差の説明因子となり得ることが示された。地域差や人種差に着目した新たな膠芽腫臨床試験デザインや新規治療の開発が期待される。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (11 results)

All 2019 2018 2017

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (10 results) (of which Int'l Joint Research: 3 results)

  • [Journal Article] Distribution differences in prognostic copy number alteration profiles in IDH-wild-type glioblastoma cause survival discrepancies across cohorts2019

    • Author(s)
      Umehara Toru、Arita Hideyuki、Yoshioka Ema、Shofuda Tomoko、Kanematsu Daisuke、Kinoshita Manabu、Kodama Yoshinori、Mano Masayuki、Kagawa Naoki、Fujimoto Yasunori、Okita Yoshiko、Nonaka Masahiro、Nakajo Kosuke、Uda Takehiro、Tsuyuguchi Naohiro、Fukai Junya、Fujita Koji、Kishima Haruhiko、Kanemura Yonehiro et al.
    • Journal Title

      Acta Neuropathologica Communications

      Volume: 7 Issue: 1 Pages: 131-131

    • DOI

      10.1186/s40478-019-0749-8

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 初発IDH野生型膠芽腫におけるNFKBIA欠失の臨床的意義の検討2019

    • Author(s)
      梅原徹、有田英之、吉岡絵麻,、正札智子、木下学,、児玉良典、香川尚己、沖田典子、埜中正博、宇田武弘、深井順也、藤田浩二、阪本大輔、森艦二、貴島晴彦、金村米博
    • Organizer
      日本脳神経外科学会第78回学術総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 機械学習による画像テクスチャ解析を用いた初発膠芽腫の予後推定2019

    • Author(s)
      梅原徹、木下学、佐々木貴浩、有田英之、吉岡絵麻、正札智子、平山龍一、木嶋教行、香川尚己、沖田典子、宇田武弘、深井順也、森艦二、貴島晴彦、金村米博
    • Organizer
      第37回日本脳腫瘍学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Interregional differences in Distribution of Prognostic Copy Number Alterations in IDH-wild-type Glioblastoma2019

    • Author(s)
      Toru Umehara, Hideyuki Arita, Ema Yoshioka, Tomoko Shofuda, Daisuke Kanematsu, Manabu Kinoshita, et al.
    • Organizer
      2019 Congress of Neurological Surgeons Annual Meeting
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A combination of MGMT methylation and NFKBIA copy number alteration refines prognostication of IDH-wt glioblastomas2019

    • Author(s)
      Toru Umehara, Hideyuki Arita, Ema Yoshioka, Tomoko Shofuda, Manabu Kinoshita, Yoshinori Kodama, Naoki Kagawa, Yoshiko Okita, Masahiro Nonaka, Takehiro Uda, Junya Fukai, Daisuke Sakamoto, Kanji Mori, Haruhiko Kishima, Yonehiro Kanemura
    • Organizer
      Society for Neuro-Oncology 24th Annual meeting
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 「再発」グリオーマ摘出術の意義 IDH1変異が「消失」した症例の分子系統解析から2018

    • Author(s)
      梅原 徹、有田英之、阿知波孝宗、横田千里、香川尚己、藤本康倫、金村米博、貴島晴彦
    • Organizer
      第23回日本脳腫瘍の外科学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 「再発」グリオーマの系統解析 IDH1変異が「消失」した症例の解析より2018

    • Author(s)
      梅原 徹、有田英之、香川尚己、藤本康倫、金村米博、貴島晴彦
    • Organizer
      第36回日本脳腫瘍病理学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 関西中枢神経腫瘍分子診断ネットワークにおける初発膠芽腫の遺伝子異常2018

    • Author(s)
      梅原 徹、有田英之、吉岡絵麻、正札智子、木下 学、児玉良典、香川尚己、藤本康倫、沖田典子、埜中正博、宇田武弘、深井順也、藤田浩二、阪本大輔、森 艦二、貴島晴彦、金村米博
    • Organizer
      日本脳神経外科学会第77回学術総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 膠芽腫におけるコピー数異常プロファイルの臨床的意義の検討2018

    • Author(s)
      梅原 徹、有田英之、吉岡絵麻、正札智子、木下 学、児玉良典、香川尚己、藤本康倫、沖田典子、埜中正博、宇田武弘、深井順也、藤田浩二、阪本大輔、森 艦二、貴島晴彦、金村米博
    • Organizer
      第36回日本脳腫瘍学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] The landscape of somatic mutations and copy number alterations in primary glioblastoma in Japan2018

    • Author(s)
      Umehara T, Arita H, Yoshioka E, Shofuda T, Kinoshita M, Kodama Y, Kagawa N, Fujimoto Y, Okita Y, Nonaka M, Uda T, Fukai J, Fujita K, Sakamoto D, Mori K, Kishima H, Kanemura Y
    • Organizer
      Society for Neuro-Oncology 23rd Annual meeting
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Grade II-III神経膠腫再発・悪性転化に対するベバジスマブの治療成績の検討2017

    • Author(s)
      梅原 徹、有田英之、金村米博、香川尚己、藤本康倫、貴島晴彦
    • Organizer
      第35回日本脳腫瘍学会学術集会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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