Identification of genomic aberrations responsible for chemosensitivity of anti-cancer drugs

• Project/Area Number: 21200001
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research a proposed research project)
• Allocation Type: Single-year Grants
• Research Field: ゲノム情報科学; Bioinformatics/Life informatics
• Research Institution: Oita University
• Principal Investigator: MORIYAMA Masatsugu 大分大学, 医学部, 教授 (90239707)
• Co-Investigator(Kenkyū-buntansha): SHIRAO Kuniaki 大分大学, 医学部, 教授 (10467996) ; TAKEUCHI Ichiro 名古屋工業大学, 工学(系)研究科(研究院), 准教授 (40335146)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥30,420,000 (Direct Cost: ¥23,400,000、Indirect Cost: ¥7,020,000); Fiscal Year 2011: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000); Fiscal Year 2010: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000); Fiscal Year 2009: ¥10,660,000 (Direct Cost: ¥8,200,000、Indirect Cost: ¥2,460,000)
• Keywords: バイオインフォマティクス / アレイCGH / メチル化 / トランスクリプトーム / microRNA / 抗がん剤感受性 / がん化学療法 / バイオインフォーマテイクス

Research Abstract

We analyzed genomic aberrations (gene copy number aberrations, aberrant expressions of mRNA and microRNA) of gastric carcinomas, renal cell carcinomas and colon carcinomas using microarray. Our study revealed that 1) miR-375 is a tumor suppressor microRNA of gastric carcinoma; 2) Upregulated miR-210 in renal cell carcinomas brought about aneuploidy to carcinoma cells; and 3) Sav1 gene is a tumor suppressor gene of renal cell carcinoma.

Research Products

• [Journal Article] Integrated analysis of genetic and epigenetic alterations reveals CpG island methylator phenotype associated with distinct clinical characters of lung adenocarcinoma. (2012)
  • Author(s): Shinjo K, Okamoto Y, An B, Yokoyama T, Takeuchi I, Fujii M, Osada H, Usami N, Hasegawa Y, Ito H, Hida T, Fujimoto N, Kishimoto T, Sekido Y, Kondo Y.
  • Journal Title: Carcinogenesis Volume: (Epub ahead of print)
• [Journal Article] Pharmacokinetic parameters from 3-Tesla DCE-MRI as surrogate biomarkers of antitumor effects of bevacizumab plus FOLFIRI in colorectal cancer with liver metastasis. (2012)
  • Author(s): Hirashima Y, Yamada Y, Tateishi U, Kato K, Miyake M, Horita Y, Akiyoshi K, Takashima A, Okita N, Takahari D, Nakajima T, Hamaguchi T, Shimada Y, Shirao K.
  • Journal Title: Int J Cancer. Volume: 130(10) Pages: 2359-65
• [Journal Article] Genomic profiling of renal cell carcinoma in patients with end-stage renal disease. (2012)
  • Author(s): Inoue T, Matsuura K, Yoshimoto T, Nguyen LT, Tsukamoto Y, Nakada C, Hijiya N, Narimatsu T, Nomura T, Sato F, Nagashima Y, Kashima K, Hatakeyama S, Ohyama C, Numakura K, Habuchi T, Nakagawa M, Seto M, Mimata H, Moriyama M.
  • Journal Title: Cancer Sci. Volume: 103(3) Pages: 569-76
• [Journal Article] Genomic profiling of renal cell carcinoma in patients with end-stage renal disease (2012)
  • Author(s): Inoue T, et al
  • Journal Title: Cancer science Volume: 103 Issue: 3 Pages: 569-576
  • DOI: 10.1111/j.1349-7006.2011.02176.x
  • Peer Reviewed
• [Journal Article] Aberrant DNA methylation associated with aggressiveness of gastrointestinal stromal tumor (2012)
  • Author(s): Y Okamoto, et al
  • Journal Title: GUT Volume: Vol.61, no.3 Pages: 392-401
  • Peer Reviewed
• [Journal Article] Epigenetic subclassification of meningiomas based on genome-wide DNA methylation analyses (2012)
  • Author(s): Kishida Y, et al
  • Journal Title: Carcinogenesis Volume: vol.32, no.2 Pages: 436-441
  • Peer Reviewed
• [Journal Article] Pharmacokinetic parameters from 3-Tesla DCE-MRI as surrogate biomarkers of antitumor effects of bevacizumab plus FOLFIRI in colorectal cancer with liver metastasis (2012)
  • Author(s): Hirashima Y, et al
  • Journal Title: International Journal of Cancer Volume: 130(10) Pages: 2359-2365
  • Peer Reviewed
• [Journal Article] Evaluation of safety, pharmacokinetics, and efficacy of vorinostat, a histone deacetylase inhibitor, in the treatment of gastrointestinal (GI) cancer in a phase I clinical trial (2012)
  • Author(s): Doi T, et al
  • Journal Title: Int J Clin Oncol Volume: (in Press)
  • Peer Reviewed
• [Journal Article] Downregulation of SAV1 plays a role in pathogenesis of high-grade clear cell renal cell carcinoma. (2011)
  • Author(s): Matsuura K, Nakada C, Mashio M, Narimatsu T, Yoshimoto T, Tanigawa M, Tsukamoto Y, Hijiya N, Takeuchi I, Nomura T, Sato F, Mimata H, Seto M, Moriyama M.
  • Journal Title: BMC Cancer Volume: 11 Pages: 523-523
• [Journal Article] Identification of FOXO3 and PRDM1 as tumor-suppressor gene candidates in NK-cell neoplasms by genomic and functional analyses. (2011)
  • Author(s): Karube K, Nakagawa M, Tsuzuki S, Takeuchi I, Honma K, Nakashima Y, Shimizu N, Ko YH, Morishima Y, Ohshima K, Nakamura S, Seto M.
  • Journal Title: Blood. Volume: 118(12) Pages: 3195-204
• [Journal Article] A phase II study of biweekly mitomycin C and irinotecan combination therapy in patients with fluoropyrimidine-resistant advanced gastric cancer: a report from the Gastrointestinal Oncology Group of the Japan Clinical Oncology Group (JCOG0109-DI Trial). (2011)
  • Author(s): Hamaguchi T, Shirao K, Ohtsu A, Hyodo I, Arai Y, Takiuchi H, Fujii H, Yoshida M, Saito H, Denda T, Koizumi W, Iwase H, Boku N; Gastrointestinal Oncology Study Group of Japan Clinical Oncology Group.
  • Journal Title: Gastric Cancer. Volume: 14(3) Pages: 226-33
• [Journal Article] Aberrant DNA methylation status of endometriosis: epigenetics as the pathogenesis, biomarker and therapeutic target. (2011)
  • Author(s): Nasu K, Kawano Y, Tsukamoto Y, Takano M, Takai N, Li H, Furukawa Y, Abe W, Moriyama M, Narahara H.
  • Journal Title: J Obstet Gynaecol Res. Volume: 37(7) Pages: 683-95
• [Journal Article] Genomic profiling of submucosal-invasive gastric cancer by array-based comparative genomic hybridization. (2011)
  • Author(s): Kuroda A, Tsukamoto Y, Nguyen LT, Noguchi T, Takeuchi I, Uchida M, Uchida T, Hijiya N, Nakada C, Okimoto T, Kodama M, Murakami K, Matsuura K, Seto M, Ito H, Fujioka T, Moriyama M.
  • Journal Title: PLoS One. Volume: 6(7)
• [Journal Article] Overexpression of miR-210, a downstream target of HIF1α, causes centrosome amplification in renal carcinoma cells. (2011)
  • Author(s): Nakada C, Tsukamoto Y, Matsuura K, Nguyen TL, Hijiya N, Uchida T, Sato F, Mimata H, Seto M, Moriyama M.
  • Journal Title: J Pathol. Volume: 224(2) Pages: 280-8
• [Journal Article] Overexpression of miR-210, a downstream target of HIF1α, causes centrosome amplification in renal carcinoma cells (2011)
  • Author(s): Nakada C, et al
  • Journal Title: J Pathol Volume: 224 Issue: 2 Pages: 280-8
  • DOI: 10.1002/path.2860
  • Peer Reviewed
• [Journal Article] Genomic profiling of submucosal-invasive gastric cancer by array-based comparative genomic hybridization (2011)
  • Author(s): Kuroda A, et al
  • Journal Title: PLoS One Volume: 6
  • Peer Reviewed
• [Journal Article] Visinin-like protein-1 overexpression is an indicator of lymph node metastasis and poor prognosis in colorectal cancer patients (2011)
  • Author(s): Akagi T, et al
  • Journal Title: Int J Cancer Volume: (published on line) Issue: 6 Pages: 1307-1317
  • DOI: 10.1002/ijc.27341
  • Peer Reviewed
• [Journal Article] Downregulation of sav1 plays a role in pathogenesis of high-grade clear cell renal cell carcinoma (2011)
  • Author(s): Matsuura K, et al
  • Journal Title: BMC cancer Volume: 11 Issue: 1 Pages: 523-523
  • DOI: 10.1186/1471-2407-11-523
  • Peer Reviewed
• [Journal Article] Nonlinear Regularization Path for Quadratic Loss Support Vector Machines (2011)
  • Author(s): M Karasuyama, I Takeuchi
  • Journal Title: IEEE Transactions on Neural Networks Volume: vol.22, no.10 Pages: 1613-1625
  • Peer Reviewed
• [Journal Article] Identification of FOXO3 and PRDM1 as tumor suppressor gene candidates in NK cell neoplasms by genomic and functional analyses (2011)
  • Author(s): K Karube, et al
  • Journal Title: Blood Volume: vol.118, no.12 Pages: 3195-3204
  • Peer Reviewed
• [Journal Article] NeuroD1 Downregulates Slit2 Expression and Promotes Cell Motility and Tumor Formation of Neuroblastoma (2011)
  • Author(s): P Huang, et al
  • Journal Title: Cancer Research Volume: vol.71, no.8 Pages: 2938-2948
  • Peer Reviewed
• [Journal Article] Characteristics and Outcomes of Patients With Advanced Gastric Cancer Who Declined to Participate in a Randomized Clinical Chemotherapy Trial (2011)
  • Author(s): Tanai C, et al
  • Journal Title: JOURNAL OF ONCOLOGY PRACTICE Volume: 7(3) Pages: 148-154
  • Peer Reviewed
• [Journal Article] Feasibility study of adjuvant chemotherapy with S-1 plus cisplatin for gastric cancer (2011)
  • Author(s): Takahari D, et al
  • Journal Title: Cancer Chemother Pharmacol Volume: 67(6) Pages: 1423-1428
  • Peer Reviewed
• [Journal Article] Ectopic Hapatocellular Carcinoma at Left Sub-Diaphragm with Lung Metastasis (2011)
  • Author(s): NishikawaK, et al
  • Journal Title: Internal Medicine Volume: 50(14) Pages: 1505-1506
  • Peer Reviewed
• [Journal Article] Neuroendocrine tumors of the stomach : chemotherapy with cisplatin plus irinotecan is effective for gastric poorly-differentiated neuroendocrine carcinoma (2011)
  • Author(s): Okita NT, et al
  • Journal Title: Gastric Cancer Volume: 14(2) Pages: 161-165
  • Peer Reviewed
• [Journal Article] A phase II study of biweekly mitomycin C and irinotecan combination therapy in patients with fluoropyrimidine-resistant advanced gastric cancer : a report from the Gastrointestinal Oncology Group of the Japan Clinical Oncology Group (JCOG0109-DI Trial) (2011)
  • Author(s): Hamaguchi T, et al
  • Journal Title: Gastric Cancer Volume: 14 Pages: 226-233
  • Peer Reviewed
• [Journal Article] Characteristics and Outcomes of Patients With Advanced Gastric Cancer Who Declined to Participate in a Randomized Clinical Chemotherapy Trial (2011)
  • Author(s): Tanai T, et al
  • Journal Title: JOURNAL OF ONCOLOGY PRACTICE Volume: 7(3) Pages: 148-153
  • Peer Reviewed
• [Journal Article] Overexpression of miR-210, a downstream molecule of HIF1α, causes centrosome amplification in renal carcinoma cells. (2011)
  • Author(s): Nakada C, et al.
  • Journal Title: The Journal of Pathology Volume: (In Press)
  • Peer Reviewed
• [Journal Article] The alpha-lipoic acid derivative sodium zinc dihydrolipoylhistidinate reduces chemotherapy-induced alopecia in a rat model : a pilot study. (2011)
  • Author(s): Hagiwara S
  • Journal Title: Surgery Today Volume: (In Press)
  • Peer Reviewed
• [Journal Article] Novel target genes responsive to the anti-growth activity of triptolide in endometrial and ovarian cancer cells. (2010)
  • Author(s): Li H, Takai N, Yuge A, Furukawa Y, Tsuno A, Tsukamoto Y, Kong S, Moriyama M, Narahara H.
  • Journal Title: Cancer Lett. Volume: 297(2) Pages: 198-206
• [Journal Article] Vesicocutaneous fistula formation during treatment with sunitinib malate: Case report. (2010)
  • Author(s): Watanabe K, Otsu S, Morinaga R, Kawano S, Hirashima Y, Sakashita H, Shirao K.
  • Journal Title: BMC Gastroenterol Volume: 10 Pages: 128-128
• [Journal Article] Second-line chemotherapy with irinotecan plus cisplatin after the failure of S-1 monotherapy for advanced gastric cancer. (2010)
  • Author(s): Takahari D, Shimada Y, Takeshita S, Nishitani H, Takashima A, Okita N, Hirashima Y, Kato K, Hamaguchi T, Yamada Y, Shirao K.
  • Journal Title: Gastric Cancer Volume: 13(3) Pages: 186-90
• [Journal Article] Genomic profiling of gastric carcinoma in situ and adenomas by array-based comparative genomic hybridization. (2010)
  • Author(s): Uchida M, Tsukamoto Y, Uchida T, Ishikawa Y, Nagai T, Hijiya N, Nguyen LT, Nakada C, Kuroda A, Okimoto T, Kodama M, Murakami K, Noguchi T, Matsuura K, Tanigawa M, Seto M, Ito H, Fujioka T, Takeuchi I, Moriyama M.
  • Journal Title: J Pathol. Volume: 221(1) Pages: 96-105
• [Journal Article] MicroRNA-375 is downregulated in gastric carcinomas and regulates cell survival by targeting PDK1 and 14-3-3zeta. (2010)
  • Author(s): Tsukamoto Y, Nakada C, Noguchi T, Tanigawa M, Nguyen LT, Uchida T, Hijiya N, Matsuura K, Fujioka T, Seto M, Moriyama M.
  • Journal Title: Cancer Res. Volume: 70(6) Pages: 2339-49
• [Journal Article] Analysis of p53 mutations and the expression of p53 and p21WAF1/CIP1 protein in 15 cases of sebaceous carcinoma of the eyelid. (2010)
  • Author(s): Kiyosaki K, Nakada C, Hijiya N, Tsukamoto Y, Matsuura K, Nakatsuka K, Daa T, Yokoyama S, Imaizumi M, Moriyama M.
  • Journal Title: Invest Ophthalmol Vis Sci. Volume: 51(1) Pages: 7-11
• [Journal Article] Invasive carcinomas originating from intraductal papillary mucinous neoplasms of the pancreas : conspicuity sites of the solid masses on triple-phase dynamic CT imaging. (2010)
  • Author(s): Yamada Y
  • Journal Title: Abdom Imaging Volume: 35 Pages: 181-188
  • Peer Reviewed
• [Journal Article] MicroRNA-375 is down-regulated in gastric carcinomas and regulates cell survival by targeting PDK1 and 14-3-3ζ-- (2010)
  • Author(s): Yoshiyuki Tsukamoto^<**>, Chisato Nakada^<**>, Tsuyoshi Noguchi, Masato Tanigawa, Nguyen Lam Tung, Tomohisa Uchida, Naoki Hijiya, Keiko Matsuura, Toshio Fujioks, Masao Seto, Masatsugu Moriyama^*.
  • Journal Title: Cancer Research 70 Pages: 2339-2349
  • Peer Reviewed
• [Journal Article] Genomic profiling of gastric carcinoma in situ and adenomas by array-based comparative genomic hybridization. (2010)
  • Author(s): Masahiro Uchida, Yoshiyuki Tsukamoto, Tomohisa Uchida, Yuta Ishikawa, Takayuki Nagai, Naoki Hijiya, Lam Tung Nguyen, Chisato Nakada, Akiko Kuroda, Tadayoshi Okimoto, Masaaki Kodama, Kazunari Murakami, Tsuyoshi Noguchi, Keiko Matsuura, Masato Tanigawa, Masao Seto, Hisao Ito, Toshio Fujioka, Ichiro Takeuchi, Masatsugu Moriyama^*.
  • Journal Title: Journal of Pathology 221 Pages: 96-105
  • Peer Reviewed
• [Journal Article] Analysis of virulence factors of Helicobacter pylori isolated from a Vietnamese population. (2009)
  • Author(s): Uchida T, Nguyen LT, Takayama A, Okimoto T, Kodama M, Murakami K, Matsuhisa T, Trinh TD, Ta L, Ho DQ, Hoang HH, Kishida T, Fujioka T, Moriyama M, Yamaoka Y.
  • Journal Title: BMC Microbiol. Volume: 9 Pages: 175-175
• [Journal Article] The potential of copy number gains and losses, detected by array-based comparative genomic hybridization, for computational differential diagnosis of B-cell lymphomas and genetic regions involved in lymphomagenesis. (2009)
  • Author(s): Takeuchi I, Tagawa H, Tsujikawa A, Nakagawa M, Katayama-Suguro M, Guo Y, Seto M.
  • Journal Title: Haematologica Volume: 94(1) Pages: 61-9
• [Journal Article] Array comparative genomic hybridization analysis of PTCL-U reveals a distinct subgroup with genetic alterations similar to lymphoma-type adult T-cell leukemia/lymphoma. (2009)
  • Author(s): Nakagawa M, Nakagawa-Oshiro A, Karnan S, Tagawa H, Utsunomiya A, Nakamura S, Takeuchi I, Ohshima K, Seto M.
  • Journal Title: Clin Cancer Res. Volume: 15(1) Pages: 30-8
• [Presentation] Target neighbor consistent feature weighting for nearest neighbor classification (2011)
  • Author(s): I Takeuchi, M Sugiyama
  • Organizer: 25th Annual Conference on Neural Information Processing Systems (NIPS2011)
  • Place of Presentation: グラナダ、スペイン
  • Year and Date: 2011-12-13
• [Presentation] 腎淡明細胞癌におけるmiR-210過剰発現の意義 (2011)
  • Author(s): 中田知里, ほか
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2011-10-04
• [Presentation] high gradeの淡明腎細胞癌ではHippoシグナルの異常がみられる (2011)
  • Author(s): 松浦恵子, ほか
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2011-10-03
• [Presentation] 胃癌におけるマイクロRNA発現 (2011)
  • Author(s): 成松隆弘, ほか
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2011-10-03
• [Presentation] Multi-parametric solution path algorithm for instance-weighted support vector machine (2011)
  • Author(s): M Karasuyama, N Harada, M Sugiyama, I Takeuchi
  • Organizer: 2011 IEEE International Workshop on Machine Learning for Signal Processing (MLSP2011)
  • Place of Presentation: 北京、中国
  • Year and Date: 2011-09-21
• [Presentation] Suboptimal solution path algorithm for support vector machine (2011)
  • Author(s): M Karasuyama, I Takeuchi
  • Organizer: The 28th International Conference on Machine Learning (ICML2011)
  • Place of Presentation: Bellevue Washington, USA
  • Year and Date: 2011-07-01
• [Presentation] 胃癌におけるマイクロRNA発現 (2011)
  • Author(s): 塚本善之、守山正胤
  • Organizer: 第100回日本病理学会総会
  • Place of Presentation: パシフィコ横浜(招待講演)
  • Year and Date: 2011-04-28
• [Presentation] Genomic profiling of gastric carcinoma in situ and adenomas by array-based comparative genomic hybridization (2011)
  • Author(s): 塚本善之, ほか
  • Organizer: 102th AACR
  • Place of Presentation: オーランド、フロリダ
  • Year and Date: 2011-04-05
• [Presentation] Biological effect of miR-210 overexpression on renal carcinoma cells (2011)
  • Author(s): 中田知里, ほか
  • Organizer: 102th AACR
  • Place of Presentation: オーランド、フロリダ
  • Year and Date: 2011-04-03
• [Presentation] GENOMIC COPY NUMBER LOSS AT 9P IS ASSOCIATED WITH METASTASIS OF RENAL CELL CARCINOMA (2011)
  • Author(s): 成松隆弘, ほか
  • Organizer: AUA 2011
  • Place of Presentation: ワシントンD.C.
• [Presentation] 胃癌で発現低下するmiR-375はPDK1と14-3-3ζを標的として細胞生存を制御する (2010)
  • Author(s): 塚本善之
  • Organizer: 第69回 日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2010-09-22
• [Presentation] 胃癌転移と9pゲノムコピー数異常の関係 (2010)
  • Author(s): 成松隆弘
  • Organizer: 第69回 日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2010-09-22
• [Presentation] 粘膜下浸潤胃癌のアレイCGH解析 (2010)
  • Author(s): 黒田明子
  • Organizer: 第69回 日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2010-09-22
• [Presentation] Array-CGH法による口腔扁平上皮癌のゲノム異常解析 (2010)
  • Author(s): 吉岡俊一
  • Organizer: 第69回 日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2010-09-22
• [Presentation] 終末期腎に生じた腎癌のアレイCGH解析 (2010)
  • Author(s): 井上亨
  • Organizer: 第69回 日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2010-09-22