Identification of the genomic alterations in metastatic renal cell carcinoma.

• Project/Area Number: 24590416
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Oita University
• Principal Investigator: MORIYAMA Masatsugu 大分大学, 医学部, 教授 (90239707)
• Co-Investigator(Kenkyū-buntansha): NAKADA Chisato 大分大学, 医学部, 助教 (60379625)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 腎細胞癌 / 転移 / 遺伝子 / 腎細胞がん / がん抑制遺伝子 / 腎がん / ゲノム異常 / アレイCGH

Outline of Final Research Achievements

We performed array CGH analysis to analyze the genomic profiles of 20 cases of primary ccRCC and their corresponding metastases. We identified 32 chromosomal regions in which gene copy number alterations were detected more frequently in metastases than in the primary tumors. Among these 32 regions, 9p24.1-p13.3 loss was the most statistically significant alteration. Transcriptome analysis revealed that 2 out of 58 genes located at 9p24.1-p13.3 were downregulated due to gene copy number loss in ccRCCs. Reexpression of these 2 genes in ccRCC cell lines revealed that downregulation of NDUFB6 due to loss at 9p24.1-p13.3 may confer a growth advantage on metastatic ccRCC cells. On the basis of our present data, we propose that NDUFB6 is a possible tumor suppressor of metastatic ccRCCs.

Research Products

• [Journal Article] Downregulation of NDUFB6 due to 9p24.1-p13.3 loss is implicated in metastatic clear cell renal cell carcinoma. (2015)
  • Author(s): Narimatsu T, *Matsuura K, Nakada C, Tsukamoto Y, Hijiya N, Kai T, Inoue T, Uchida T, Nomura T, Sato F, Seto M, Takeuchi I, Mimata H, Moriyama M
  • Journal Title: Cancer Medicine Volume: 4(1) Issue: 1 Pages: 112-124
  • DOI: 10.1002/cam4.351
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Clear cell papillary renal cell carcinoma: a review. (2014)
  • Author(s): Kuroda N, Ohe C, Kawakami F, Mikami S, Furuya M, Matsuura K, Moriyama M, Nagashima Y, Zhou M, Petersson F, López JI, Hes O, Michal M, Amin MB.
  • Journal Title: Int J Clin Exp Pathol Volume: 7 Pages: 7312-8
  • Peer Reviewed / Open Access
• [Journal Article] Genomic profiling of oral squamous cell carcinomaby array-based comparative genomic hybridization (2013)
  • Author(s): Yoshioka S, Tsukamoto Y, Hijiya N, Nakada C, Uchida T, Matsuura K, Takeuchi I, Seto M, Kawano K, Moriyama M
  • Journal Title: PLoS One Volume: 8(2) Issue: 2 Pages: 56165-56165
  • DOI: 10.1371/journal.pone.0056165
  • Peer Reviewed
• [Journal Article] MiR-29c is downregulated in gastric carcinomas and regulates cell proliferation by targeting RCC2 (2013)
  • Author(s): Matsuo M, Nakada C, Tsukamoto Y, Noguchi T, Uchida T, Hijiya N, Matsuura K, Moriyama M
  • Journal Title: Mol Cancer Volume: 12 Issue: 1 Pages: 15-15
  • DOI: 10.1186/1476-4598-12-15
  • Peer Reviewed
• [Presentation] SAV1 inhibits renal tumor growth in xenograft model (2014)
  • Author(s): 甲斐友喜、松浦恵子、中田知里、塚本善之、守山正胤ほか
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: 横浜パシフィコ（神奈川県横浜市）
  • Year and Date: 2014-09-25 – 2014-09-27
• [Remarks] 国立大学法人大分大学医学部分子病理学講座ホームページ
  • URL: http://www.med.oita-u.ac.jp/byori2/index.htm