Comprehensive investigation of tumorigenesis mechanism induced by sarcoma-related fusion genes
Project/Area Number |
18H02677
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Basic Section 50010:Tumor biology-related
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Research Institution | National Cancer Center Japan |
Principal Investigator |
Kohsaka Shinji 国立研究開発法人国立がん研究センター, 研究所, ユニット長 (00627119)
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Co-Investigator(Kenkyū-buntansha) |
椨 康一 東京医科歯科大学, 難治疾患研究所, 助教 (10466469)
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Project Period (FY) |
2018-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2019: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2018: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
|
Keywords | 肉腫 / 融合遺伝子 / 機能解析 / バイオマテリアル |
Outline of Final Research Achievements |
Sarcoma-related fusion genes were integrated into 3T3, C2C12 and mouse mesenchymal stem cells and abilities of cell proliferation and differentiation inhibition were evaluated. Parental cells and oncogenic cells were labeled with individual fluorescent proteins and seeded on polymer slides to identify synthetic polymers on which oncogenic cells grow rapidly or attach strongly compared with parental cells. Established oncogenic cells were performed RNA-seq and conducted clustering analysis and Gene Set Enrichment Analysis to identify gene sets and signaling pathways specifically affected by respective fusion genes. Candidate molecular targeted drugs having specific inhibitory effects on fusion-introduced cells were screened and validated by individual drug sensitivity assay.
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Academic Significance and Societal Importance of the Research Achievements |
融合遺伝子特異的な遺伝子発現パターンが同定され, 融合遺伝子横断的な分類がすすみ, 融合遺伝子を標的とした分子標的薬の創薬に向けた分子プロファイリングの基盤が構築された. また融合遺伝子導入細胞特異的に増殖・接着する合成ポリマーが同定され, がん化や薬剤耐性などの細胞機能のスクリーニングに適したマテリアルの開発につながることが期待される.
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Report
(4 results)
Research Products
(63 results)
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[Journal Article] Rapid reprogramming of tumour cells into cancer stem cells on double-network hydrogels2021
Author(s)
Suzuka J, Tsuda M, Wang L, Kohsaka S, Kishida K, Semba S, Sugino H, Aburatani S, Frauenlob M, Kurokawa T, Kojima S, Ueno T, Ohmiya Y, Mano H, Yasuda K, Gong JP, Tanaka S
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Journal Title
Nat Biomed Eng
Volume: -
Issue: 8
Pages: 914-925
DOI
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Peer Reviewed / Open Access
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[Journal Article] The initial assessment of expert panel performance in core hospitals for cancer genomic medicine in Japan2021
Author(s)
Sunami K, Naito Y, Aimono E, Amano T, Ennishi D, Kage H, Kanai M, Komine K, Koyama T, Maeda T, Morita S, Sakai D, Kohsaka S, Tsuchihara K, Yoshino T
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Journal Title
Int J Clin Oncol
Volume: 26
Issue: 3
Pages: 443-449
DOI
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Peer Reviewed / Open Access
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[Journal Article] Development of an optimal protocol for molecular profiling of tumor cells in pleural effusions at single-cell level2021
Author(s)
Takeda Nakamura I, Ikegami M, Hasegawa N, Hayashi T, Ueno T, Kawazu M, Yagishita S, Goto Y, Shinno Y, Kojima Y, Takamochi K, Takahashi F, Takahashi K, Mano H, Kohsaka S
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Journal Title
Cancer Sci
Volume: -
Issue: 5
Pages: 2006-2019
DOI
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Peer Reviewed / Open Access
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[Journal Article] Comprehensive molecular and clinicopathological profiling of desmoid tumours2021
Author(s)
Kohsaka Shinji、Hirata Makoto、Ikegami Masachika、Ueno Toshihide、Kojima Shinya、Sakai Tomohisa、Ito Kan、Naka Norifumi、Ogura Koichi、Kawai Akira、Iwata Shintaro、Okuma Tomotake、Yonemoto Tsukasa、Kobayashi Hiroshi、Suehara Yoshiyuki、Hiraga Hiroaki、Kawamoto Teruya、Motoi Toru、Oda Yoshinao、Matsubara Daisuke、etc
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Journal Title
European Journal of Cancer
Volume: 145
Pages: 109-120
DOI
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Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] RET inhibition in novel patient-derived models of RET-fusion positive lung adenocarcinoma reveals a role for MYC upregulation2020
Author(s)
Hayashi T, Odintsov I, Smith RS, Ishizawa K, Liu AJW, Delasos L, Kurzatkowski C, Tai H, Gladstone E, Vojnic M, Kohsaka S, Suzawa K, Liu Z, Kunte S, Mattar MS, Khodos I, Davare MA, Drilon A, Cheng E, Stanchina E, Ladanyi M, Somwar R
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Journal Title
Dis Model Mech
Volume: -
Issue: 2
Pages: 1-11
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Peer Reviewed / Open Access
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[Journal Article] Clinical practice guidance for next-generation sequencing in cancer diagnosis and treatment (edition 2)2020
Author(s)
Naito Y, Aburatani H, Amano T, Baba E, Furukawa T, Hayashida T, Hiyama E, Ikeda S, Kanai M, Kato M, Kinoshita I, Kiyota N, Kohno T, Kohsaka S, et al.
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Journal Title
Int J Clin Oncol
Volume: -
Issue: 2
Pages: 233-283
DOI
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Peer Reviewed / Open Access
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[Journal Article] Identification of a Novel MAN1A1-ROS1 Fusion Gene Through mRNA-based Screening for Tyrosine Kinase Gene Aberrations in a Patient with Leiomyosarcoma2020
Author(s)
Suehara Y, Kohsaka S, Hayashi T, Akaike K, Kurisaki-Arakawa A, Sato S, Kobayashi E, Mizuno S, Ueno T, Morii T, Okuma T, Kurihara T, Hasegawa N, Sano K, Sasa K, Okubo T, Kim Y, Mano H, Saito T
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Journal Title
Clin Orthop Relat Res
Volume: -
Issue: 4
Pages: 838-852
DOI
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Peer Reviewed / Open Access
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[Journal Article] Diffuse expression of MUC6 defines a distinct clinicopathological subset of pulmonary invasive mucinous adenocarcinoma2020
Author(s)
Kishikawa S, Hayashi T, Saito T, Takamochi K, Kohsaka S, Sano K, Sasahara N, Sasa K, Kurihara T, Hara K, Suehara Y, Takahashi F, Suzuki K, Yao T
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Journal Title
Mod Pathol
Volume: -
Issue: 4
Pages: 786-797
DOI
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Peer Reviewed / Open Access
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[Journal Article] Clinicopathological characteristics of lung adenocarcinoma with compound EGFR mutations.2020
Author(s)
Hayashi T, Kohsaka S, Takamochi K, Hara K, Kishikawa S, Sano K, Takahashi F, Suehara Y, Saito T, Takahashi K, Suzuki K, Yao T.
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Journal Title
Human Pathology
Volume: 14
Pages: 42-51
DOI
Related Report
Peer Reviewed
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[Journal Article] High-throughput functional evaluation of BRCA2 variants of unknown significance.2020
Author(s)
Ikegami, M., Kohsaka, S., Ueno, T., Momozawa, Y., Inoue, S., Tamura, K., Shimomura, A., Hosoya, N., Kobayashi, H., Tanaka, S., Mano, H.
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Journal Title
Nature Communications
Volume: 11
Issue: 1
Pages: 2573-2573
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Identification of Novel CD74-NRG2α Fusion From Comprehensive Profiling of Lung Adenocarcinoma in Japanese Never or Light Smokers2020
Author(s)
Kohsaka S, Hayashi T, Nagano M, Ueno T, Kojima S, Kawazu M, Shiraishi Y, Kishikawa S, Suehara Y, Takahashi F, Takahashi K, Suzuki K, Takamochi K, Mano H
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Journal Title
Journal of Thoracic Oncology
Volume: -
Issue: 6
Pages: 30098-8
DOI
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Peer Reviewed / Open Access
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[Journal Article] Spinal solitary fibrous tumor of the neck: Next-generation sequencing-based analysis of genomic aberrations.2020
Author(s)
Ando M, Kobayashi H, Shinozaki-Ushiku A, Chikuda H, Matsubayashi Y, Yoshida M, Saito Y, Kohsaka S, Oda K, Miyagawa K, Aburatani H, Mano H, Yamasoba T.
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Journal Title
Auris Nasus Larynx.
Volume: Epub ahead of print
Issue: 6
Pages: 1058-1063
DOI
Related Report
Peer Reviewed
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[Journal Article] Activation of insulin-like growth factor-1 receptor confers acquired resistance to osimertinib in non-small cell lung cancer with EGFR T790M mutation2020
Author(s)
Hayakawa D, Takahashi F, Mitsuishi Y, Tajima K, Hidayat M, Winardi W, Ihara H, Kanamori K, Matsumoto N, Asao T, Ko R, Shukuya T, Takamochi K, Hayashi T, Suehara Y, Takeda Nakamura I, Ueno T, Kohsaka S, Mano H, Takahashi K
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Journal Title
Thorac Cancer
Volume: 11
Issue: 1
Pages: 140-149
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Detection of circulating sarcoma tumor cells using a microfluidic chip-type cell sorter.2019
Author(s)
Hasegawa N, Takeda Nakamura I, Ueno T, Kojima S, Kawazu M, Akaike K, Okubo T, Takagi T, Suehara Y, Hayashi T, Saito T, Kaneko K, Mano H, Kohsaka S.
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Journal Title
Sci Rep.
Volume: 9
Issue: 1
Pages: 20047-20047
DOI
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Peer Reviewed / Open Access
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[Journal Article] Protein Expression Profiles Corresponding to Histological Changes with Denosumab Treatment in Giant Cell Tumors of Bone.2019
Author(s)
Suehara Y, Okubo T, Kurihara T, Hayashi T, Kohsaka S, Kazuno S, Sano K, Hasegawa N, Miura Y, Akaike K, Kim Y, Takamochi K, Takahashi F, Ueno T, Kaneko K, Saito T.
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Journal Title
Proteomics Clin Appl
Volume: 13
Issue: 5
Pages: 1800147-1800147
DOI
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Peer Reviewed
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[Journal Article] Proteomic signatures corresponding to the SS18/SSX fusion gene in synovial sarcoma.2018
Author(s)
Ishii M, Suehara Y, Sano K, Kohsaka S, Hayashi T, Kazuno S, Akaike K, Mukaihara K, Kim Y, Okubo T, Takamochi K, Takahashi F, Kaneko K, Saito T.
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Journal Title
Oncotarget
Volume: 9(101)
Issue: 101
Pages: 37509-37519
DOI
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Peer Reviewed / Open Access
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[Journal Article] PPP2R1A regulated by PAX3/FOXO1 fusion contributes to the acquisition of aggressive behavior in PAX3/FOXO1-positive alveolar rhabdomyosarcoma.2018
Author(s)
Akaike K, Suehara Y, Kohsaka S, Hayashi T, Tanabe Y, Kazuno S, Mukaihara K, Toda-Ishii M, Kurihara T, Kim Y, Okubo T, Hayashi Y, Takamochi K, Takahashi F, Kaneko K, Ladanyi M, Saito T.
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Journal Title
Oncotarget
Volume: 9(38)
Issue: 38
Pages: 25206-25215
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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