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Analysis of genomic and epigenomic intratumoral heterogeneity reveals mechanisms of resistance to chemoradiotherapy in esophageal cancer

Research Project

Project/Area Number 16K10397
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Radiation science
Research InstitutionKyushu University

Principal Investigator

HIRATA Hidenari  九州大学, 大学病院, 医員 (90721267)

Co-Investigator(Kenkyū-buntansha) 新井田 厚司  東京大学, 医科学研究所, 助教 (00772493)
平川 雅和  九州大学, 大学病院, 准教授 (20380454)
三森 功士  九州大学, 大学病院, 教授 (50322748)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2017: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000)
Fiscal Year 2016: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Keywords化学放射線耐性 / ゲノム / エピゲノム / 腫瘍内不均一性 / 食道癌 / 放射線腫瘍学 / 化学放射線治療耐性 / 放射線腫瘍額
Outline of Final Research Achievements

We analyzed genomic intratumor heterogeneity of esophageal cancer to investigate the mechanisms of resistance to chemoradiotherapy (CRT). DNA was extracted from malti-sampling pre-treatment tumor tissues, recurrent tumor tissues, and paired peripheral normal blood from three patients with local recurrence after CRT. Each sample was subjected to multi-region whole exome sequencing. Pre-treatment and recurrent tumors showed a distinct genomic alterations. Analyzing genomic intratumor heterogeneity, we found intrinsic alterations involved in CRT in esophageal cancer.

Academic Significance and Societal Importance of the Research Achievements

化学放射線治療(chemoradiotherapy, 以下CRT)は食道癌への有効な治療の一つだが、再発する症例をしばしば経験する。ひとつの癌の内部における遺伝子異常の不均一な分布(腫瘍内均一性)が治療抵抗性にかかわることがしれており、本研究では食道癌のCRT抵抗性の原因となる腫瘍内均一性の様相を捉えた。治療標的となる遺伝子異常の発見は治療方法の開発につながると予想され、その社会的意義は多大である。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (14 results)

All 2019 2018 2017 2016

All Journal Article (2 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (12 results) (of which Int'l Joint Research: 2 results,  Invited: 4 results)

  • [Journal Article] Additional radiotherapy following endoscopic submucosal dissection for T1a-MM/T1b-SM esophageal squamous cell carcinoma improves locoregional control.2018

    • Author(s)
      Hisano O, Nonoshita T, Hirata H, Sasaki T, Watanabe H, Wakiyama H, Ono M, Ohga S, Honda H.
    • Journal Title

      Radiation Oncology

      Volume: 29 Issue: 1 Pages: 14-14

    • DOI

      10.1186/s13014-018-0960-y

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The loss of CASP4 expression is associated with poor prognosis in esophageal squamous cell carcinoma2017

    • Author(s)
      Shibamoto M, Hirata H, Eguchi H, Sawada G, Sakai N, Kajiyama Y, Mimori K
    • Journal Title

      Oncology Letters

      Volume: 13 Issue: 3 Pages: 1761-6

    • DOI

      10.3892/ol.2017.5646

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] ゲノム医療時代における放射線治療の役割2019

    • Author(s)
      平田秀成
    • Organizer
      第9回日本放射線腫瘍学会放射線生物学セミナー
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Mutational Dynamics of Primary and Recurrent Esophageal Squamous Cell Carcinoma Treated with Chemoradiotherapy2018

    • Author(s)
      Hirata H, Ohga S, Niida A, Yoshitake T,Asai K, Nakashima T,Tsurumaru D, Nishimuta Y, Muraki T, Sasaki T, Nomoto S, Mimori K, Honda H
    • Organizer
      60th American Society for Radiation Oncology Annual Meeting
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 放射線治療におけるがんゲノム解析を用いたprecision medicine2018

    • Author(s)
      平田秀成
    • Organizer
      第16回日本臨床腫瘍学会学術集会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 全エクソームシーケンスが明らかにした食道癌の化学放射線耐性にかかわる体細胞変異2018

    • Author(s)
      平田秀成、大賀才路、新井田厚司、吉武忠正、浅井佳央里、松本圭司、中島孝彰、 鶴丸大介、西牟田雄祐、村木俊夫、佐々木智成、野元諭、三森功士、本田浩
    • Organizer
      日本放射線腫瘍学会第31回学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Somatic Copy Number Alterations Associate with Chemoradiotherapy Response in Esophageal Squamous Cell Carcinoma2018

    • Author(s)
      Hirata H, Ohga S, Niida A, Saito T, Tsurumaru D, Mimori K, Honda H.
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 食道癌に対する化学放射線療法症例における再発クローンの検討2018

    • Author(s)
      平田 秀成、新井田 厚司、大賀 才路、吉武 忠正、浅井 佳央里、松本 圭司、 中島 孝彰、鶴丸 大介、野元 諭、三森 功士、本田 浩
    • Organizer
      第56回日本放射線腫瘍学会生物部会学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] バイオインフォマティクスによる 放射線生物学の革新2018

    • Author(s)
      平田秀成
    • Organizer
      第8回放射線生物学セミナー
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Genome-wide Copy Number Analysis of Chemoradiotherapy Response in Esophageal Squamous Cell Carcinoma.2016

    • Author(s)
      Hirata H, Niida A, Ito S, Uchi R, Saito T, Terashima K, Ohga S, Sakamoto K, Hirakawa M, Honda H, Mimori K.
    • Organizer
      The 1st Meeting of the Federaion of Asian Organization for Radiation Oncology
    • Place of Presentation
      Kyoto
    • Year and Date
      2016-11-25
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Genomic correlates of response to chemoradio-therapy in esophageal squamous cell carcinoma.2016

    • Author(s)
      Hirata H, Ito S, Niida A, Uchi R, Saito T, Masuda T, Hayashi N, Kuroda Y, Eguchi H, Hirakawa M, Honda H, Mimori K
    • Organizer
      第75回日本癌学会学術総会
    • Place of Presentation
      横浜市
    • Year and Date
      2016-10-06
    • Related Report
      2016 Research-status Report
  • [Presentation] 肝癌におけるFructose-1,6-biphosphatase発現異常と腫瘍進展・糖代謝異常の検討2016

    • Author(s)
      平田 秀成, 杉町 圭史, 小松 久晃, 増田 隆明, 林 直樹, 江口 英利, 伊藤修平, 平川 雅和, 本田 浩, 三森 功士
    • Organizer
      第25回 日本癌病態治療研究会
    • Place of Presentation
      千葉市
    • Year and Date
      2016-06-08
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] 食道癌・肝癌ゲノムの多様性とトランスオミックス解析2016

    • Author(s)
      平田 秀成
    • Organizer
      平成28年度がんゲノム・エピゲノム、数理統計解析についての勉強会
    • Place of Presentation
      別府市
    • Related Report
      2016 Research-status Report
  • [Presentation] マルチサンプリング解析における統計解析 少ない症例数における統計学的処理について2016

    • Author(s)
      平田 秀成、齋藤 衆子
    • Organizer
      次世代シークエンス解析における統計・バイオインフォマティクス研究会
    • Place of Presentation
      東京都
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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