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

2011 Fiscal Year Final Research Report

• 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
• 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

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] 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
• [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) Pages: e22313
• [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] 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
• [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] 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
• [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