Molecular Analysis of Rare Renal Cell Carcinoma and Identification of Molecular Therapeutic Targets

• Project/Area Number: 23659752
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Urology
• Research Institution: Akita University
• Principal Investigator: HABUCHI Tomonori 秋田大学, 医学(系)研究科(研究院), 教授 (00293861)
• Co-Investigator(Kenkyū-buntansha): OHYAMA Chikara 弘前大学, 医学系研究科, 教授 (80282135) ; MIMATA Hiromitsu 大分大学, 医学部, 教授 (60219714) ; NARITA Shintaro 秋田大学, 医学部, 講師 (40396552) ; NANJO Hiroshi 秋田大学, 医学部, 准教授 (70250892)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 腎細胞癌 / Xp転座型腎細胞癌 / TFE3 / FISH / 分子標的薬 / 紡錘型腎細胞癌 / Xp転座型腎癌 / 紡錘型腎癌

Research Abstract

Molecular mechanisms of common renal cell carcinoma have been delineated by recent extensive studies. On the other hand, molecular mechanisms remain largely unknown regarding renal cell carcinoma with Xp-translocation, which is rather frequent in young patients. We tried to delineate the molecular mechanisms underlying renal cell carcinoma with Xp-translocation and to identify molecular therapeutic targets in this multi-institutional study.
By analyzing 280 patients with renal cell carcinoma, we found that 4.3% of renal cell carcinoma was immunohistologically positive for TFE3 protein. By establishing TFE3-gene FISH, we showed that most of TFE-positive tumors harbor Xp-translocation. Finally, we analyzed the clinical and pathological data of the patients with FISH-positive tumors.

Research Products

• [Journal Article] Organ-specific and tumor-size-dependent responses to sunitinib in clear cell renal cell carcinoma (2014)
  • Author(s): Tsuchiya N, Yuasa T, Maita S, Narita S, Inoue T, Numakura K, Saito M, Satoh S, Yonese J, Habuchi T
  • Journal Title: BMC Urology Volume: 14 Issue: 1 Pages: 26-26
  • DOI: 10.1186/1471-2490-14-26
  • Peer Reviewed
• [Journal Article] Serum N-glycan alteration associated with renal cell carcinoma detected by high-throughput glycan analysis. (2014)
  • Author(s): Hatakeyama S, Amano M, Tobisawa Y, Yoneyama T, Tsuchiya N, Habuchi T, Nishimura SI, Ohyama C
  • Journal Title: J Urol. Volume: 191 Issue: 3 Pages: 805-813
  • DOI: 10.1016/j.juro.2013.10.052
  • Peer Reviewed / Open Access
• [Journal Article] Insulin-like growth factor-1 genotypes and haplotypes influence the survival of prostate cancer patients with bone metastasis at initial diagnosis (2013)
  • Author(s): Tsuchiya N, Narita S, Inoue T, Saito M, Numakura K, Huang M, Hatakeyama S, Satoh S, Saito S, Ohyama C, Arai Y, Ogawa O, Habuchi T
  • Journal Title: BMC Cancer Volume: 25;13 Pages: 150-150
• [Journal Article] Risk factors for sorafenib-induced high-grade skin rash in Japanese patients with advanced renal cell carcinoma (2013)
  • Author(s): Tsuchiya N, Narita S, Inoue T, Hasunuma N, Numakura K, Horikawa Y, Satoh S, Notoya T, Fujishima N, Hatakeyama S, Ohyama C, Habuchi T
  • Journal Title: Anticancer Drugs Volume: 24(3) Pages: 310-4
• [Journal Article] A meta-analysis of genome-wide association studies to identify prostate cancer susceptibility loci associated with aggressive and non-aggressive disease (2013)
  • Author(s): Amin Al Olama A
  • Journal Title: Hum Mol Genet Volume: 22 Issue: 2 Pages: 408-415
  • DOI: 10.1093/hmg/dds425
  • Peer Reviewed
• [Journal Article] Antitumor effect of sunitinib against skeletal metastatic renal cell carcinoma through inhibition of osteoclast function (2012)
  • Author(s): Maita S, Yuasa T, Tsuchiya N, Mitobe Y, Narita S, Horikawa Y, Hatake K, Fukui I, Kimura S, Maekawa T, Habuchi T
  • Journal Title: Int J Cancer Volume: 130(3) Issue: 3 Pages: 677-84
  • DOI: 10.1002/ijc.26034
• [Journal Article] MUC1 carrying core 2 O-glycans functions as a molecular shield against NK cell attack, promoting bladder tumor metastasis (2012)
  • Author(s): Suzuki Y, et al.
  • Journal Title: International Journal of Onocology Volume: (未定)(in press) Pages: 1831-1838
  • DOI: 10.3892/ijo.2012.1411
  • Peer Reviewed
• [Journal Article] Clinical efficacy and prognostic factors for overall survival in Japanese patients with metastatic renal cell cancer treated with sunitinib (2012)
  • Author(s): Yuasa T, Tsuchiya N, Urakami S, Horikawa Y, Narita S, Inoue T, Saito M, Yamamoto S, Yonese J, Fukui I, Nakano K, Takahashi S, Hatake K, Habuchi T.
  • Journal Title: BJU Int Volume: 109(9) Pages: 1349-54
• [Journal Article] Common variants at 11q12, 10q26 and 3p11.2 are associated with prostate cancer susceptibility in Japanese (2012)
  • Author(s): 赤松秀輔, 他
  • Journal Title: Nature Genetics Volume: 44 Issue: 4 Pages: 426-429
  • DOI: 10.1038/ng.1104
  • Peer Reviewed
• [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] Reproducibility, performance, and clinical utility of a genetic risk prediction model for prostate cancer in Japanese. (2012)
  • Author(s): 赤松秀輔
  • Journal Title: Plos One Volume: 7 Issue: 10 Pages: 46454-46454
  • DOI: 10.1371/journal.pone.0046454
  • Peer Reviewed
• [Journal Article] Prognostic Factors for Overall Survival in Japanese Patients with Metastatic Renal Cell Cancer Treated with Sunitinib (2012)
  • Author(s): Yuasa T, et al
  • Journal Title: BJU int. Volume: 130 Issue: 9 Pages: 677-84
  • DOI: 10.1111/j.1464-410x.2011.10534.x
  • Peer Reviewed
• [Journal Article] A case study of metastatic Xp11.2 translocation renal cell carcinoma effectively treated with sunitinib (2011)
  • Author(s): Numakura K, Tsuchiya N, Yuasa T, Saito M, Obara T, Tsuruta H, Narita S, Horikawa Y, Satoh S, Habuchi T
  • Journal Title: Int J Clin Oncol Volume: 16(5) Issue: 5 Pages: 577-80
  • DOI: 10.1007/s10147-010-0154-6
  • NAID: 10030246990
• [Presentation] Aberrant glycosylation of N-glycan on Immunoglobulin closely relates survival of the patients with in renal cell carcinoma (2013)
  • Author(s): Shingo Hatakeyama; Yuki Tobisawa; Tohru Yoneyama; Yuichiro Suzuki; Hayato Yamamoto; Kazuyuki Mori; Takahiro Yoneyama; Yasuhiro Hashimoto; Takuya Koie; Norihiko Tsuchiya; Tomonori Habuchi; Maho Amano; Shin-Ichiro Nishimura; Chikara Ohyama
  • Organizer: American Urological Association Annual Meeting 2013
  • Place of Presentation: San Diego, CA, USA
• [Presentation] Evaluating the Association among the Pharmacokinetics of Sunitinib, its Adverse Events and the Treatment Outcomes in Advanced Renal Cell Carcinoma (2013)
  • Author(s): Norihiko Tsuchiya; Nobuhiro Fujiyama; Shintaro Narita; Takamitsu Inoue; Kazuyuki Numakura; Susumu Akihama; Mitsuru Saito; Shigeru Satoh; Masatomo Miura; Tomonori Habuchi
  • Organizer: American Urological Association Annual Meeting 2013
  • Place of Presentation: San Diego, CA, USA
• [Presentation] Organ-Specific and Size-Dependent Response to Sunitinib in Clear Cell Renal Cell Carcinoma Lesions (2013)
  • Author(s): Norihiko Tsuchiya; Takeshi Yuasa; Shinya Maita; Shintaro Narita; Takamitsu Inoue; Kazuyuki Numakura; Mitsuru Saito; Mingguo Huang; Shigeru Satoh; Tomonori Habuchi
  • Organizer: American Urological Association Annual Meeting 2013
  • Place of Presentation: San Diego, CA, USA
• [Presentation] Stimulation of macrophage inhibitory cytokine-1 by palmitic acid activates prostate cancer cell invasiveness (2012)
  • Author(s): Mingguro, H., Narita, S., Maita, S., Numakura, K., Obara, T., Inoue, T., Horikawa, Y., Satoh, S.and Habuchi, T
  • Organizer: The 107th annual meeting of the American Urological Association
  • Place of Presentation: Atlanta, USA
• [Presentation] Risk factors for sorafenib-induced erythema multiforme in Japanese patients with advanced renal cell carcinoma (2012)
  • Author(s): Tsuchiya, N., Narita, S., Inoue, T., Hasunuma, N., Numakura, K., Horikawa, Y., Satoh, S., Notoya, T., Fujishima, N., Hatakeyama, S., Ohyama, C., Habuchi, T
  • Organizer: The 32nd Congress of the Societe Internationale d'Urologie
  • Place of Presentation: Fukuoka, Japan
• [Presentation] 腎細胞癌患者におけるソラフェニブによる多形紅斑とHLA型との関連性の検討 (2012)
  • Author(s): 土谷順彦,堀川洋平,成田伸太郎,井上高光,小原崇,沼倉一幸,米田真也,佐藤滋,能登谷武,藤島直仁,藤山信弘,三浦昌朋,畠山真吾,大山力,羽渕友則
  • Organizer: 第100回日本泌尿器科学会総会
  • Place of Presentation: 横浜
• [Presentation] 転移性腎細胞癌に対するmTOR inhibitor を含むSequential Therapy の経験 (2012)
  • Author(s): 井上高光、米田真也、沼倉一幸、小原 崇、成田伸太郎、堀川洋平、土谷順彦、佐藤 滋、羽渕友則
  • Organizer: 第100回日本泌尿器科学会総会
  • Place of Presentation: 横浜
• [Presentation] Clinical Characteristics of Xp11.2 Translocation Renal Cell Carcinoma in Japanese Adult Patients (2011)
  • Author(s): Numakura, K., Tsuchiya, N., Yuasa, T., Inoue, T., Narita, S., Horikawa, Y., Hatakeyama, S., Ohyama, C., Inoue, T., Mimata, H., Saito, H., Arai, Y., Kanno, T., Kamba, T., Ogawa, O., Habuchi, T
  • Organizer: The 106th Annunal Meeting of the American Urological Association
  • Place of Presentation: Washisnton DC, USA
• [Presentation] Xp11.2 転座をともなう腎細胞癌 (2011)
  • Author(s): 沼倉一幸、土谷順彦、畠山真吾、大山 力、井上 亨、三股浩光、齋藤英郎、荒井陽一、寒野 徹、神波大己、小川 修、羽渕友則
  • Organizer: 第76回日本泌尿器科学会東部総会
  • Place of Presentation: 横浜
• [Presentation] 分子標的薬時代の腎癌の治療戦略 -Sequential に使いこなす- (2011)
  • Author(s): 羽渕友則
  • Organizer: 第63回日本泌尿器科学会西日本総会
  • Place of Presentation: 久留米市
• [Presentation] CLINICAL CHARACTERISTICS OF XP11.2 TRANSLOCATION RENAL CELL CARCINOMA IN ADULT JAPANESE PATIENTS (2011)
  • Author(s): Kazuyuki Numakura, et al
  • Organizer: Annual Meeting of American Urological Association
  • Place of Presentation: Wshington DC, USA
• [Remarks]
  • URL: http://www.med.akita-u.ac.jp/~hinyoki/default.html
• [Remarks] 秋田大学大学院医学系研究科 腎泌尿器科学講座
  • URL: http://www.med.akita-u.ac.jp/~hinyoki/
• [Remarks] 秋田大学大学院 腎泌尿器科学講座 ホームページ
  • URL: http://www.med.akita-u.ac.jp/~hinyoki/default.html
• [Remarks]
  • URL: http://www.med.akita-u.ac.jp/~hinyoki/default.html