2017 Fiscal Year Annual Research Report
Systematic and integrative analysis of the occurrence of genetic heterogeneity in CRC
Publicly Offered Research
| Project Area | Conquering cancer through neo-dimensional systems understanding |
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| Project/Area Number |
16H01576
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| Research Institution | Kyushu University |
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Principal Investigator |
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 – 2018-03-31
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| Keywords | fractile / 多様性 / PDX / 選択圧 |
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| Outline of Annual Research Achievements |
われわれはこれまでの研究結果(Uchi et al. 2016 PLoS Genet.)から、我々は「腫瘍内遺伝学的不均一性は、大腸癌の成長に伴って常に生み出され続ける。その分布は全体と部分が相似している(fractal)」という仮説を立てた。本研究では、PDXマウスモデル及びLaser Micro dissection(LMD)法を駆使し、次世代シークエンサーによるエキソームシークエンスを行うことで、この仮説を検証した。1）大腸癌の症例集積とPDXマウスモデルの作成：九州大学病院別府病院外科にて手術を行った進行大腸癌症例２例において、摘出後の大腸癌原発巣組織を一部採取し、NOD/SCIDマウスの皮下に腫瘍組織を移植することでPDXマウスモデルを作成した。この際、同時に正常大腸組織の一箇所、大腸癌原発巣組織の複数箇所より組織を採取し冷凍保存した。マウスに移植された腫瘍が増大し、適切な容積となった時点でマウスを安楽死させ、腫瘍を摘出した。この腫瘍を更に別のマウスに移植することを繰り返し、経時的に腫瘍を採取した。１症例目では順調に腫瘍組織の採取を行ったが、２症例目では組織の生着が見られず、実験を中止した。2）DNA抽出と全エキソームシークエンス：1.で得られた正常大腸組織、大腸癌組織及びマウスに移植して得られた大腸癌組織計１３検体よりgenomic DNAを抽出し、全エキソームシークエンシングを行った。１３検体全てにおいてシークエンスが終了し、現在遺伝子変異について解析を終えた。その結果、継代を経る毎に多様性が失われ、収束していることを明らかにした。
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| Research Progress Status |
29年度が最終年度であるため、記入しない。
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| Strategy for Future Research Activity |
29年度が最終年度であるため、記入しない。
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[Journal Article] GWAS Identifies Two Novel Colorectal Cancer Loci at 16q24.1 and 20q13.122018
Author(s)
Tanikawa C, Kamatani Y, Takahashi A, Momozawa Y, Leveque K, Nagayama S, Mimori K, Mori M, Ishii H, Inazawa J, Yasuda J, Tsuboi A, Shimizu A, Sasaki M, Yamaji T, Sawada N, Iwasaki M, Tsugane S, Naito M, Wakai K, Koyama T, Takezaki T, Yuji K, Murakami Y, Nakamura Y, Kubo M, Matsuda K
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Journal Title
Carcinogenesis.
Volume: Epub.
Pages: Epub.
DOI
Peer Reviewed
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[Journal Article] Identification of ARL4C as a Peritoneal Dissemination-Associated Gene and Its Clinical Significance in Gastric Cancer.2018
Author(s)
Hu Q, Masuda T, Sato K, Tobo T, Nambara S, Kidogami S, Hayashi N, Kuroda Y, Ito S, Eguchi H, Saeki H, Oki E, Maehara Y, Mimori K
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Journal Title
Ann Surg Oncol
Volume: 25(3)
Pages: 745-753
DOI
Peer Reviewed / Open Access
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[Journal Article] Antitumor effects of the antiparasitic agent ivermectin via inhibition of Yes-associated protein 1 expression in gastric cancer.2017
Author(s)
Nambara S, Masuda T, Nishio M, Kuramitsu S, Tobo T, Ogawa Y, Hu Q, Iguchi T, Kuroda Y, Ito S, Eguchi H, Sugimachi K, Saeki H, Oki E, Maehara Y, Suzuki A, Mimori K
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Journal Title
Oncotarget
Volume: 8(64)
Pages: 107666-107677.
DOI
Peer Reviewed / Open Access
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[Journal Article] Combined mutation of Apc, Kras and Tgfbr2 effectively drives metastasis of intestinal cancer.2017
Author(s)
Sakai E, Nakayama M, Oshima H, Kouyama Y, Niida A, Fujii S, Ochiai A, Nakayama KI, Mimori K, Suzuki Y, Hong CP, Ock CY, Kim SJ, Oshima M
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Journal Title
Cancer Res.
Volume: canres.3303
Pages: canres.3303.
DOI
Peer Reviewed / Open Access
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[Journal Article] Circulating exosomal microRNA-203 is associated with metastasis possibly via inducing tumor-associated macrophages in colorectal cancer.2017
Author(s)
Takano Y, Masuda T, Iinuma H, Yamaguchi R, Sato K, Tobo T, Hirata H, Kuroda Y, Nambara S, Hayashi N, Iguchi T, Ito S, Eguchi H, Ochiya T, Yanaga K, Miyano S, Mimori K
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Journal Title
Oncotarget
Volume: 8(45)
Pages: 78598-78613
DOI
Peer Reviewed / Open Access
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[Journal Article] Japanese genome-wide association study identifies a significant colorectal cancer susceptibility locus at chromosome 10p142017
Author(s)
Takahashi Y, Sugimachi K, Yamamoto K, Niida A, Shimamura T, Sato T, Watanabe M, Tanaka J, Kudo S, Sugihara K, Hase K, Kusunoki M, Yamada K, Shimada Y, Moriya Y, Suzuki Y, Miyano S, Mori M, Mimori K
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Journal Title
Cancer Sci.
Volume: 108(11)
Pages: 2239-2247
DOI
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[Journal Article] Clinical significance of ZNF750 gene expression, a novel tumor suppressor gene, in esophageal squamous cell carcinoma2017
Author(s)
Nambara S, Masuda T, Tobo T, Kidogami S, Komatsu H, Sugimachi K, Saeki H, Oki E, Maehara Y, Mimori K
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Journal Title
Oncol Lett
Volume: 14(2)
Pages: 1795-1801
DOI
Peer Reviewed / Open Access
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[Journal Article] Phosphoserine Phosphatase Is a Novel Prognostic Biomarker on Chromosome 7 in Colorectal Cancer2017
Author(s)
Sato K, Masuda T, Hu Q, Tobo T, Kidogami S, Ogawa Y, Saito T, Nambara S, Komatsu H, Hirata H, Sakimura S, Uchi R, Hayashi N, Iguchi T, Eguchi H, Ito S, Nakagawa T, Mimori K
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Journal Title
Anticancer Res.
Volume: 37(5)
Pages: 2365-2371
Peer Reviewed
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[Journal Article] Up-regulation of SLC9A9 Promotes Cancer Progression and Is Involved in Poor Prognosis in Colorectal Cancer.2017
Author(s)
Ueda M, Iguchi T, Masuda T, Komatsu H, Nambara S, Sakimura S, Hirata H, Uchi R, Eguchi H, Ito S, Sugimachi K, Mizushima T, Doki Y, Mori M, Mimori K
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Journal Title
Anticancer Res.
Volume: 37(5)
Pages: 2255-2263
Peer Reviewed
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[Journal Article] Overexpression of heat-shock factor 1 is associated with a poor prognosis in esophageal squamous cell carcinoma2017
Author(s)
Tsukao Y, Yamasaki M, Miyazaki Y, Makino T, Takahashi T, Kurokawa Y, Miyata H, Nakajima K, Takiguchi S, Mimori K, Mori M, Doki Y
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Journal Title
Oncol Lett.
Volume: 13(3)
Pages: 1819-1825.
DOI
Peer Reviewed / Open Access
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[Journal Article] Altered Expression of Hippo Signaling Pathway Molecules in Intrahepatic Cholangiocarcinoma2017
Author(s)
Sugimachi K, Nishio M, Aishima S, Kuroda Y, Iguchi T, Komatsu H, Hirata H, Sakimura S, Eguchi H, Bekki Y, Takenaka K, Maehara Y, Suzuki A, Mimori K
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Journal Title
Oncology
Volume: 93(1)
Pages: 67-74
DOI
Peer Reviewed / Open Access
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[Journal Article] MOB1-YAP1/TAZ-NKX2.1 axis controls bronchioalveolar cell differentiation, adhesion and tumour formation2017
Author(s)
Otsubo K, Goto H, Nishio M, Kawamura K, Yanagi S, Nishie W, Sasaki T, Maehama T, Nishida H, Mimori K, Nakano T, Shimizu H, Mak TW, Nakao K, Nakanishi Y, Suzuki A
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Journal Title
Oncogene.
Volume: 36(29)
Pages: 4201-4211
DOI
Peer Reviewed / Open Access
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[Journal Article] Clinical Significance of FANCD2 Gene Expression and its Association with Tumor Progression in Hepatocellular Carcinoma2017
Author(s)
Komatsu H, Masuda T, Iguchi T, Nambara S, Sato K, Hu Q, Hirata H, Ito S, Eguchi H, Sugimachi K, Eguchi H, Doki Y, Mori M, Mimori K
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Journal Title
Anticancer Res.
Volume: 37(3)
Pages: 1083-1090
Peer Reviewed
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[Journal Article] Clinical Impact of Tumor-Infiltrating Lymphocytes in Esophageal Squamous Cell Carcinoma.2017
Author(s)
Sudo T, Nishida R, Kawahara A, Saisho K, Mimori K, Yamada A, Mizoguchi A, Kadoya K, Matono S, Mori N, Tanaka T, Akagi Y
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Journal Title
Ann Surg Oncol.
Volume: 24(12)
Pages: 3763-3770
DOI
Peer Reviewed / Open Access
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[Journal Article] Downregulation of ST6GALNAC1 is associated with esophageal squamous cell carcinoma development2017
Author(s)
Iwaya T, Sawada G, Amano S, Kume K, Ito C, Endo F, Konosu M, Shioi Y, Akiyama Y, Takahara T, Otsuka K, Nitta H, Koeda K, Mizuno M, Nishizuka S, Sasaki A, Mimori K
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Journal Title
Int J Oncol
Volume: 50(2)
Pages: 441-447
DOI
Peer Reviewed / Open Access
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[Journal Article] The Expression of CCAT2, a Novel Long Noncoding RNA Transcript, and rs6983267 Single-Nucleotide Polymorphism Genotypes in Colorectal Cancers.2017
Author(s)
Kasagi Y, Oki E, Ando K, Ito S, Iguchi T, Sugiyama M, Nakashima Y, Ohgaki K, Saeki H, Mimori K, Maehara Y
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Journal Title
Oncology.
Volume: 92(1)
Pages: 48-54
DOI
Peer Reviewed / Open Access
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[Journal Article] Attenuated RND1 Expression Confers Malignant Phenotype and Predicts Poor Prognosis in Hepatocellular Carcinoma.2017
Author(s)
Komatsu H, Iguchi T, Masuda T, Hirata H, Ueda M, Kidogami S, Ogawa Y, Sato K, Hu Q, Nambara S, Saito T, Sakimura S, Uchi R, Ito S, Eguchi H, Sugimachi K, Eguchi H, Doki Y, Mori M, Mimori K
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Journal Title
Ann Surg Oncol.
Volume: 24(3)
Pages: 850-859
DOI
Peer Reviewed / Open Access
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[Journal Article] As a Novel Prognostic Marker, Cysteine/histidine-rich 1 (CYHR1) is a Therapeutic Target in Patients with Esophageal Squamous Cell Carcinoma2017
Author(s)
Desaki R, Sawada G, Okumura H, Ikeda R, Tanabe K, Komatsu H, Mimori K, Mori M, Kita Y, Uchikado Y, Arigami T, Uenosono Y, Owaki T, Ishigami S, Natsugoe S
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Journal Title
Ann Surg Oncol.
Volume: 24(2)
Pages: 586-593
DOI
Peer Reviewed / Open Access
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