Identification of a molecular target of colorectal cancers with associated copy number aberrations between two different chromosomal loci.

• Project/Area Number: 26670608
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Kyushu University
• Principal Investigator: Mimori Koshi 九州大学, 大学病院, 教授 (50322748)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 染色体 / コピー数相関 / 癌原因子 / 選択圧 / ゲノム増幅 / 大腸癌 / メインクローン / サブクローン / ドライバー遺伝子 / TPX2 / EEM法 / MLN8237

Outline of Final Research Achievements

In our previous study (Ann Oncol 2015)，we disclosed that significant association of copy number aberrations between MYC locus 8q24 and TPX2 locus 20q11. The inhibition of TPX2 directly suppressed the proliferation of MYC driven cancers. In the current study, we initially disclosed that the combination of different loci was observed in adenomas and even in early CRC cancers. This finding indicated that the current combination might play an important role in tumorigenesis of CRC and in clinical significance as a diagnostic marker or a therapeutic target. Besides, we found another combination of different chromosomes with significant association between chromosomes, 7 and 13. We discovered an intriguing gene there, and have been focusing on the magnitude of the gene as a molecular target and a biomarker for progression of CRC cases.

Research Products

• [Journal Article] Downregulation of SIRT4 Expression Is Associated with Poor Prognosis in Esophageal Squamous Cell Carcinoma. (2016)
  • Author(s): Nakahara Y, Yamasaki M, Sawada G, Miyazaki Y, Makino T, Takahashi T, Kurokawa Y, Nakajima K, Takiguchi S, Mimori K, Mori M, Doki Y.
  • Journal Title: Oncology. Volume: Epub
  • Peer Reviewed / Open Access
• [Journal Article] Integrated Molecular Profiling of Human Gastric Cancer Identifies DDR2 as a Potential Regulator of Peritoneal Dissemination (2016)
  • Author(s): Kurashige J, Hasegawa T, Niida A, Sugimachi K, Deng N, Mima K, Uchi R, Sawada G, Takahashi Y, Eguchi H, Inomata M, Kitano S, Fukagawa T, Sasako M, Sasaki H, Sasaki S, Mori M, Yanagihara K, Baba H, Miyano S, Tan P, Mimori K.
  • Journal Title: Sci Rep. Volume: 6 Issue: 1 Pages: 22371-22371
  • DOI: 10.1038/srep22371
  • NAID: 120006352400
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Clinical and biological significance of circulating tumor cells in cancer. (2016)
  • Author(s): Masuda T, Hayashi N, Iguchi T, Ito S, Eguchi H, Mimori K.
  • Journal Title: Mol Oncol. Volume: 10 Issue: 3 Pages: 408-17
  • DOI: 10.1016/j.molonc.2016.01.010
  • Peer Reviewed / Open Access
• [Journal Article] Genomic Landscape of Esophageal Squamous Cell Carcinoma in a Japanese Population. (2016)
  • Author(s): G. Sawada (他43名, 山本21番目)
  • Journal Title: Gastroenterology Volume: 150 Issue: 5 Pages: 1171-1182
  • DOI: 10.1053/j.gastro.2016.01.035
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Clinical and biological significance of transcription termination factor, RNA polymerase I in human liver hepatocellular carcinoma. (2016)
  • Author(s): Komatsu H, Iguchi T, Ueda M, Nambara S, Saito T, Hirata H, Sakimura S1, Takano Y1, Uchi R1, Shinden Y, Eguchi H, Masuda T, Sugimachi K, Eguchi H, Doki Y, Mori M, Mimori K.
  • Journal Title: Oncol Rep Volume: 35 Issue: 4 Pages: 2073-80
  • DOI: 10.3892/or.2016.4593
  • Peer Reviewed / Open Access
• [Journal Article] An Integrative Analysis to Identify Driver Genes in Esophageal Squamous Cell Carcinoma (2015)
  • Author(s): Sawada G, Niida A, Hirata H, Komatsu H, Uchi R, Shimamura T, Takahashi Y, Kurashige J, Matsumura T, Ueo H, Takano Y, Ueda M, Sakimura S, Shinden Y, Eguchi H, Sudo T, Sugimachi K, Yamasaki M, Tanaka F, Tachimori Y, Kajiyama Y, Natsugoe S, Fujita H, Tanaka Y, Calin G, Miyano S, Doki Y, Mori M, Mimori K
  • Journal Title: PLoS One Volume: 10(10) Issue: 10 Pages: e0139808-e0139808
  • DOI: 10.1371/journal.pone.0139808
  • Peer Reviewed / Open Access
• [Journal Article] Identification of Recurrence-Related microRNAs from Bone Marrow in Hepatocellular Carcinoma Patients. (2015)
  • Author(s): Sugimachi K, Sakimura S, Tomokuni A, Uchi R, Hirata H, Komatsu H, Shinden Y, Iguchi T, Eguchi H, Masuda T, Morita K, Shirabe K, Eguchi H, Maehara Y, Mori M, Mimori K
  • Journal Title: J Clin Med. Volume: 4 Issue: 8 Pages: 1600-11
  • DOI: 10.3390/jcm4081600
  • Peer Reviewed / Open Access
• [Journal Article] Exosomal microRNA in serum is a novel biomarker of recurrence in human colorectal cancer. (2015)
  • Author(s): Matsumura T, Sugimachi K, Iinuma H, Mori M, Ochiya T, Mimori K.
  • Journal Title: Br J Cancer Volume: 113(2) Issue: 2 Pages: 275-281
  • DOI: 10.1038/bjc.2015.201
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Overexpression of Transcription Termination Factor 1 is Associated with a Poor Prognosis in Patients with Colorectal Cancer. (2015)
  • Author(s): Ueda M, Iguchi T, Nambara S, Saito T, Komatsu H, Sakimura S, Hirata H, Uchi R, Takano Y, Shinden Y, Eguchi H, Masuda T, Sugimachi K, Yamamoto H, Doki Y, Mori M, Mimori K.
  • Journal Title: Ann Surg Oncol. Volume: Epub Issue: S3 Pages: 1490-1498
  • DOI: 10.1245/s10434-015-4652-7
  • Peer Reviewed / Open Access
• [Journal Article] A Long Non-coding RNA Activated by Transforming Growth Factor-β is an Independent Prognostic Marker of Gastric Cancer. (2015)
  • Author(s): Saito T, Kurashige J, Nambara S, Komatsu H, Hirata H, Ueda M, Sakimura S, Uchi R, Takano Y, Shinden Y, Iguchi T, Eguchi H, Ehata S, Murakami K, Sugimachi K, Mimori K.
  • Journal Title: Ann Surg Oncol. Volume: Epub Issue: S3 Pages: 915-922
  • DOI: 10.1245/s10434-015-4554-8
  • Peer Reviewed / Open Access
• [Journal Article] A long noncoding RNA, lncRNA-ATB, is involved in the progression and prognosis of colorectal cancer. (2015)
  • Author(s): Iguchi T, Uchi R, Nambara, Saito T, Komatsu, Hirata H, Ueda M,Sakimura S,Takano Y, Kurashige J, Shinden Y, Eguchi H, Sugimachi K, Maehara Y, Mimori K.
  • Journal Title: Anticancer Res. Volume: 35 Pages: 1385-8
  • Peer Reviewed
• [Journal Article] The AURKA/TPX2 axis drives colon tumorigenesis cooperatively with MYC. (2015)
  • Author(s): Takahashi Y, Sheridan P, Niida A, Sawada G, Uchi R, Mizuno H, Kurashige J, Sugimachi K, Sasaki S, Shimada Y, Hase K, Kusunoki M, Kudo S, Watanabe M, Yamada K, Sugihara K, Yamamoto H, Suzuki A, Doki Y, Miyano S, Mori M, Mimori K
  • Journal Title: Ann. Oncol. Volume: 26(5) Issue: 5 Pages: 935-42
  • DOI: 10.1093/annonc/mdv034
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Epigenetic modulation and repression of miR-200b by cancer-associated fibroblasts contribute to cancer invasion and peritoneal dissemination in gastric cancer. (2015)
  • Author(s): Kurashige J, Mima K, Sawada G, Takahashi Y, Eguchi H, Sugimachi K, Mori M, Yanagihara K, Yashiro M, Hirakawa K, Baba H, Mimori K.
  • Journal Title: Carcinogenesis. Volume: 36 Issue: 1 Pages: 133-41
  • DOI: 10.1093/carcin/bgu232
  • Peer Reviewed / Open Access
• [Journal Article] Significance of polypyrimidine tract binding protein 1 expression in colorectal cancer. (2015)
  • Author(s): Takahashi H, Nishimura J, Kagawa Y, Kano Y, Takahashi Y, Wu X, Hiraki M, Hamabe A, Konno M, Haraguchi N, Takemasa I, Mizushima T, Ishii M, Mimori K, Ishii H, Doki Y, Mori M, Yamamoto H.
  • Journal Title: Mol Cancer Ther Volume: epub
  • Peer Reviewed / Open Access
• [Journal Article] A Highly Accurate Inclusive Cancer Screening Test Using Caenorhabditis elegans Scent Detection (2015)
  • Author(s): Hirotsu T, Sonoda H, Uozumi T, Shinden Y,Mimori K, Maehara Y, Ueda N, Hamakawa M
  • Journal Title: PLOS ONE Volume: 10 Issue: 3 Pages: e0118699-e0118699
  • DOI: 10.1371/journal.pone.0118699
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] F-box protein FBXW7 inhibits cancer metastasis in a non-cell-autonomous manner (2015)
  • Author(s): Yumimoto, K., Akiyoshi, S., Ueo, H., Sagara, Y., Onoyama, I., Ueo, H., Ohno, S., Mori, M., Mimori, K., Nakayama, K. I.
  • Journal Title: J. Clin. Invest. Volume: 125 Issue: 2 Pages: 621-635
  • DOI: 10.1172/jci78782
  • Peer Reviewed / Open Access
• [Journal Article] Prognostic significance of high mobility group box 1 (HMGB1) expression in patients with colorectal cancer. (2014)
  • Author(s): Ueda M, Takahashi Y, Shinden Y, Sakimura S, Hirata H, Uchi R, Takano Y, Kurashige J, Iguchi T, Eguchi H, Sugimachi K, Yamamoto H, Doki Y, Mori M, Mimori K.
  • Journal Title: Anticancer Res. Volume: 34 Pages: 5357-62
  • Peer Reviewed
• [Journal Article] A single nucleotide polymorphism in fibronectin 1 determines tumor shape in colorectal cancer. (2014)
  • Author(s): Kida H, Takano Y, Yamamoto K, Mori M, Yanaga K, Tanaka J, Kudo SE, Mimori K.
  • Journal Title: Oncol Rep. Volume: 32 Issue: 2 Pages: 548-52
  • DOI: 10.3892/or.2014.3251
  • Peer Reviewed / Open Access
• [Presentation] 大腸癌のゲノム・エピゲノム解析により明らかとなった腫瘍内多様性クローン進化 (2015)
  • Author(s): 内龍太郎、高橋佑典、新井田厚司、鈴木穣、森正樹、宮野悟、三森功士
  • Organizer: 第26回日本消化器癌発生学会総会
  • Place of Presentation: 米子
  • Year and Date: 2015-11-19
• [Presentation] 大腸癌におけるmiR-146a多型の臨床的意義 (2015)
  • Author(s): 井口友宏、小松久晃、増田隆明、南原翔、齋藤衆子、上田正射、平田秀成、﨑村正太郎、内龍太郎、新田吉陽、伊藤修平、江口英利、三森功士
  • Organizer: 第74回日本がん学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-10-08
• [Presentation] 大腸癌の腫瘍内不均一性とゲノム・エピゲノムの進化 (2015)
  • Author(s): 内龍太郎、高橋佑典、新井田厚司、平田秀成、森正樹、宮野悟、三森功士
  • Organizer: 第74回日本がん学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-10-08
• [Presentation] 大腸癌原発巣から転移巣へのゲノム・エピゲノムレベルの進化 (2015)
  • Author(s): 三森功士、新井田厚司、内龍太郎、高橋佑典、森正樹，宮野悟
  • Organizer: 第24回日本がん転移学会学術集会・総会
  • Place of Presentation: 大阪
  • Year and Date: 2015-07-23
• [Presentation] 大腸癌細胞におけるPLS3は上皮間葉移行を介して肝転移を形成する (2015)
  • Author(s): 上田正射、新田吉陽、杉町圭史、三森功士
  • Organizer: 第24回日本がん転移学会学術集会・総会
  • Place of Presentation: 大阪
  • Year and Date: 2015-07-23
• [Presentation] 遺伝子多型と網羅的pathway解析による糖尿病合併症大腸発癌の危険因子の同定 (2015)
  • Author(s): 杉町圭史、山口類、上田正射、井口友宏、江口英利、調憲、宮野悟、森正樹、前原喜彦、三森功士
  • Organizer: 第70回日本消化器外科学会総会
  • Place of Presentation: 浜松
  • Year and Date: 2015-07-15
• [Presentation] 大腸癌肝転移における宿主細胞と癌細胞のmicroRNAを介した微小環境の解明 (2015)
  • Author(s): 上田正射、高野裕樹、齋藤衆子、南原翔、小松久晃、﨑村正太郎、平田秀成、内龍太郎、新田吉陽、井口友宏、江口英利、増田隆明、杉町圭史、山本浩文、土岐祐一郎、森正樹、三森功士
  • Organizer: 第36回癌免疫外科研究会
  • Place of Presentation: 奄美大島
  • Year and Date: 2015-05-14
• [Presentation] 大腸癌におけるrRNA転写因子TTF-1の臨床的意義と癌進展における役割について (2015)
  • Author(s): 上田正射、南原翔、小松久晃、高野裕樹、新田吉陽、井口友宏、江口英利、杉町圭史、土岐祐一郎、森正樹、三森功士
  • Organizer: 第115回日本外科学会定期学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-04-16
• [Presentation] 大腸癌における8q24多型と糖尿病の遺伝環境相互解析による発癌関連遺伝子の同定 (2015)
  • Author(s): 杉町圭史、上田正射、南原翔、小松久晃、高野裕樹、新田吉陽、井口友宏、山口類、新井田厚司、宮野悟、森正樹、前原喜彦、三森功士
  • Organizer: 第115回日本外科学会定期学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-04-16
• [Presentation] 大腸癌においてＴＧＦβにより活性化されるLong noncoding RNAの臨床病理学的意義 (2014)
  • Author(s): 井口友宏、内龍太郎、南原翔、齋藤衆子、小松久晃、平田秀成、上田正射、崎村正太郎、高野裕樹、藏重淳二、新田吉陽、江口英利、杉町圭史、三森功士
  • Organizer: 第25回日本消化器癌発生学会
  • Place of Presentation: 福岡
  • Year and Date: 2014-11-13 – 2014-11-14
• [Presentation] 大腸癌におけるPlastin3の過剰発現は、上皮間葉移行を介して肝転移を促進させる因子となる (2014)
  • Author(s): 上田正射、杉町圭史、崎村正太郎、平田秀成、高野裕樹、内龍太郎、藏重淳二、新田吉陽、江口英利、井口友宏、森正樹、三森功士
  • Organizer: 第73回日本癌学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] 長鎖非翻訳RNA-ATBは大腸がんにおける予後不良因子である (2014)
  • Author(s): 内龍太郎、井口友宏、藏重淳二、杉町圭史、江口英利、高野裕樹
  • Organizer: 第73回日本癌学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] 大腸癌肝転移における宿主細胞と癌細胞のmicroRNAを介した微小環境の解明 (2014)
  • Author(s): 高野裕樹、崎村正太郎、上田正射、平田秀成、藏重淳二、杉町圭史、矢永勝彦、三森功士
  • Organizer: 第73回日本癌学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] 大腸癌におけるHigh morbidity group1の発現意義について (2014)
  • Author(s): 上田正射、上尾裕紀、高野裕樹、松村多恵、藏重淳二、江口英利、主藤朝也、杉町圭史、森正樹、三森功士
  • Organizer: 第69回日本消化器外科学会総会
  • Place of Presentation: 郡山
  • Year and Date: 2014-07-16 – 2014-07-18
• [Presentation] 大腸癌幹細胞を標的にした治療法開発のための原発巣/転移巣におけるゲノム・エピゲノム解析 (2014)
  • Author(s): 三森功士、平田秀成
  • Organizer: 第43回放射線による制癌シンポジウム
  • Place of Presentation: 京都
  • Year and Date: 2014-07-11 – 2014-07-12
• [Presentation] 転移再発を決定する大腸癌細胞ー骨髄中宿主細胞間のmicroRNA/gene axis (2014)
  • Author(s): 高野裕樹、崎村正太郎、平田秀成、上田正射、内龍太郎、藏重淳二、新田吉陽、江口英利、杉町圭史、矢永勝彦、三森功士
  • Organizer: 第23回日本がん転移学会
  • Place of Presentation: 金沢
  • Year and Date: 2014-07-10 – 2014-07-11