Analysis of genomic and epigenomic intratumoral heterogeneity reveals mechanisms of resistance to chemoradiotherapy in esophageal cancer
| Project/Area Number |
16K10397
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Radiation science
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| Research Institution | Kyushu University |
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Principal Investigator |
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| 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)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| 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)
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| 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 |
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| 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.
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| 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。
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Report
(4 results)
Research Products
(14 results)
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[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
Int'l Joint Research
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[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
Int'l Joint Research
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[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
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[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
Invited
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