Establishment of new therapeutic protocol for pediatric renal tumor according to the new risk classification

2013 Fiscal Year Final Research Report

• Project/Area Number: 23390405
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatric surgery
• Research Institution: Osaka University
• Principal Investigator: FUKUZAWA Masahiro 大阪大学, その他部局等, 名誉教授 (60165272)
• Co-Investigator(Kenkyū-buntansha): OUE Takaharu 大阪大学, 医学部, 講師 (50314315) ; 金子 安比古 埼玉県立がんセンター臨床腫瘍研究所, 研究所長 (50373387) ; 野崎 美和子 獨協医科大学越谷病院, 放射線科, 教授 (30197727) ; 大喜多 肇 国立成育医療研究センター研究所, 室長 (50317260) ; 樋之津 史郎 岡山大学病院, 新医療研究開発センター, 教授 (80323567)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Keywords: 小児腎腫瘍 / 予後因子 / RASSF1A遺伝子 / WTX遺伝子 / 両側性腎芽腫 / 腎機能障害 / 治療プロトコール / 腎ラブドイド腫瘍

Research Abstract

We analyzed methylation status of tumor suppressor gene RASSF1A in 84 Wilms tumors and found out that it was significantly associated with a poor outcome. Moreover, we analyzed the mutation of WTX gene and revealed that this also was significantly associated with a poor outcome. Therefore these biomarkers were considered be candidates of the new biomarkers for risk classification to create the new therapeutic protocols.
The survival rate of bilateral Wilms tumors (BWT) has been improved; however, the results are not satisfactory in terms of the renal preservation. We reviewed the outcome of BWT registered in JWiTS. Bilateral nephron-sparing surgery (NSS) was achieved only in 10 of 28 cases (36%) and 10 children (40%) developed impaired renal function. The protocol should be changed to improve the rate of preservation of the renal parenchyma. Preoperative chemotherapy should be performed to shrink the tumors, and subsequent NSS should be carried out after a central imaging evaluation.

Research Products

• [Journal Article] Social and biological factors influencing the outcomes of children with Wilms tumors in Kenya and other Sub-Saharan countries (2014)
  • Author(s): Kumon K, Kaneko Y
  • Journal Title: Transl Pediatr Volume: 3 Pages: 42-46
  • Peer Reviewed
• [Journal Article] Bilateral Wilms tumors treated according to the Japan Wilms Tumor Study Group protocol (2014)
  • Author(s): Oue T, Koshinaga T, Okita H, Kaneko Y, Hinotsu S, Fukuzawa M
  • Journal Title: Pediatr Blood Cancer Volume: (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] RASSF1A methylation may have two biological roles in neuroblastoma tumorigenesis depending on the ploidy status and age of patients (2014)
  • Author(s): Haruta M, Kamijo T, Nakagawara A, Kaneko Y
  • Journal Title: Cancer Lett
  • DOI: 10.1016/j.canlet.2014.03.022
  • Peer Reviewed
• [Journal Article] RASSF1A methylation indicates a poor prognosis in hepatoblastoma patients (2013)
  • Author(s): Honda S, Miyagi H, Kaneko Y, (他8名)
  • Journal Title: Pediatr Surg Int Volume: 11 Pages: 1147-52
  • Peer Reviewed
• [Journal Article] DNA methylation profile distinguishes clear cell sarcoma of the kidney from other pediatric renal tumors (2013)
  • Author(s): Ueno H, Okita H, Akimoto S, Kobayashi K, Nakabayashi K, Hata K, Fujimoto J, Hata J, Fukuzawa M, Kiyokawa N
  • Journal Title: PLoS One Volume: 8(4) Pages: e62233
  • DOI: 10.1371
  • Peer Reviewed
• [Journal Article] Methylation of the RASSF1A Promoter Is Predictive of Poor Outcome among Patients with Wilms Tumor (2012)
  • Author(s): Ohshima J, Okita H, Koshinaga T, Oue T, Hinotsu S, Fukuzawa M, Kaneko Y (他7人)
  • Journal Title: Pediatric Blood Cancer Volume: 59 Pages: 499-505
  • Peer Reviewed
• [Journal Article] Different incidences of epigenetic but not genetic abnormalities between Wilms tumors in Japanese and Caucasian children (2012)
  • Author(s): Haruta M, Okita H, Fukuzawa M, Kaneko Y (他9 名)
  • Journal Title: Cancer Sci Volume: 103 Pages: 1129-1135
  • Peer Reviewed
• [Journal Article] 小児固形腫瘍の放射線治療 (2012)
  • Author(s): 野崎美和子
  • Journal Title: 臨床放射線 Volume: 57 Pages: 1321-1330
• [Journal Article] Expression of Wilms tumor 1 gene in a variety of pediatric tumors (2011)
  • Author(s): Oue T, Uehara S, Yamanaka H, Takama Y, Oji Y, Fukuzawa M
  • Journal Title: J Pediatr Surg Volume: 46 Pages: 2233-8
  • Peer Reviewed
• [Journal Article] The role of WT1 gene in neuroblastoma (2011)
  • Author(s): Wang J, Oue T, Uehara S, Yamanaka H, Oji Y, Fukuzawa M
  • Journal Title: J Pediatr Surg Volume: 46 Pages: 326-31
  • Peer Reviewed
• [Presentation] 最新放射線治療技術の小児がんへの応用・陽子線・重粒子線・IM RTの基礎・相違点 (2014)
  • Author(s): 野崎美和子
  • Organizer: 厚生労働省科学研究費ワークショップ : 小児がんの粒子線治療 : 最新の成績と臨床研究の現状小児がん粒子線治療技術の小児がんへの応用
  • Place of Presentation: 高崎
  • Year and Date: 2014-02-26
• [Presentation] Bilateral Wilms' tumors treated according to the Japan Wilms Tumor Study Group protocol (2013)
  • Author(s): Oue T, Fukuzawa M, Okita H, HorieH, Saito M, Nozaki M, Chin M, Nakadate N, Hinotsu S, Koshinaga T, Kaneko Y, Tanaka Y
  • Organizer: 45th Congress of the International Society of Paediatric Oncology
  • Place of Presentation: Hong Kong, China
  • Year and Date: 20130000
• [Presentation] 日本ウィルムス腫瘍研究グループに登録された両側性腎芽腫の検討 (2013)
  • Author(s): 大植孝治, 福澤正洋, 越永従道, 大喜多肇, 金子安比古, 堀江 弘, 斉藤正博, 野崎美和子, 陳 基明, 中館尚也, 樋之津史郎, 田中祐吉, 春田雅之, 桑島成子, 高安 肇
  • Organizer: 第55回日本小児血液・がん学会
  • Place of Presentation: 福岡
  • Year and Date: 20130000
• [Presentation] 網羅的DNA メチル化解析による腎明細胞肉腫(CCSK)の分子マーカー (2012)
  • Author(s): 上野瞳, 大喜多肇, 秋元信吾, 福澤正洋, 藤本純一郎, 秦順一, 清河信敬
  • Organizer: 第101回日本病理学会総会
  • Place of Presentation: 京王プラザホテル(東京都新宿区)
  • Year and Date: 20120426-28
• [Presentation] Current Results the Japan Wilms Tumor Study (JWiTS) and Future Protocols (2012)
  • Author(s): Oue T, Fukuzawa M, Okita H, Mugishima H, Horie H, Hata J, Saito M, Nozaki M, Chin M, Nakadate N, Hinotsu S, Koshinaga T, KanekoY, Kitano K, Tanaka Y
  • Organizer: 第54回日本小児血液・がん学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 20120000
• [Presentation] Problema of Childhood Cancer Survivers in Pediatric Surgical Clinic (2012)
  • Author(s): OueT, Uehara S, Fukuzawa M, Miyoshi Y, Ohta H, Hashii Y
  • Organizer: 44th Congress of the International Society of Paediatric Oncology
  • Place of Presentation: London, UK
  • Year and Date: 20120000
• [Presentation] 小児腎肉腫におけるDNA メチル化解析 (2011)
  • Author(s): 上野瞳, 大喜多肇, 清河信敬
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 20111213-16
• [Presentation] がん抑制遺伝子RASSF1A のプロモーターメチル化はWilms 腫瘍の予後不良因子である (2011)
  • Author(s): 大島淳二郎, 春田雅之, 渡辺直樹, 新井康仁, 寺下友佳代, 長祐子, 井口晶裕, 有賀正, 大喜多肇, 越永従道, 大植孝治, 樋之津史郎, 中舘尚也, 堀江弘, 福澤正洋, 金子安比古
  • Organizer: 第53回日本小児血液・がん学会学術集会
  • Place of Presentation: ベイシア文化ホール(群馬県)
  • Year and Date: 20111124-27
• [Presentation] 日本におけるWT1 遺伝子変異を有するウィルムス腫瘍の臨床病理学的検討 (2011)
  • Author(s): 大喜多肇, 秦順一, 柴田理恵, 高田礼子, 菊池春人, 藤本純一郎, 金子安比古, 堀江弘, 田中祐吉, 福澤正洋, 清河信敬
  • Organizer: 第100回日本病理学会総会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 20110428-30
• [Presentation] Expression of WT1 Gene in a Variety of Pediatric Tumors (2011)
  • Author(s): Oue T, Uehara S, Yamanaka H, Takama Y, Oji Y, Fukuzawa M
  • Organizer: 44th PAPS Annual Meeting
  • Place of Presentation: Cancun, Mexico
  • Year and Date: 20110000
• [Presentation] Expression of WT1 Gene in a Variety of Pediatric Tumors (2011)
  • Author(s): Oue T, Uehara S, Yamanaka H, Takama Y, Oji Y, Fukuzawa M
  • Organizer: International Surgical Week
  • Place of Presentation: Yokohama, Japan
  • Year and Date: 20110000
• [Presentation] 小児腫瘍の放射線治療 (2011)
  • Author(s): 野崎美和子
  • Organizer: 第24回日本放射線腫瘍学会
  • Place of Presentation: 神戸
  • Year and Date: 2011-11-18
• [Book] 系統小児外科学第3版(福澤正洋, 中村哲郎, 窪田昭男編), 病理組織検査法, 分子標的治療, 再生医療, 腎芽腫, 肝腫瘍, 横紋筋肉腫, 膵腫瘍, 悪性リンパ腫 (2013)
  • Author(s): 大植孝治
  • Total Pages: (72-74, 327-330, 331-336, 712-718, 719-729, 730-736, 743-746, 754-756)
  • Publisher: 永井書店
• [Book] 小児科 診断・治療指針(遠藤文夫編), Wilms腫瘍(腎芽腫) (2012)
  • Author(s): 大植孝治
  • Total Pages: 894-897
  • Publisher: 中山書店
• [Book] 別冊日本臨床 腎臓症候群(第2版)上, 腎芽腫(Wilms腫瘍) (2012)
  • Author(s): 大植孝治
  • Total Pages: 629-632
  • Publisher: 日本臨牀社
• [Book] 小児がん診療ハンドブック(堀部敬三編), 腎腫瘍 (2011)
  • Author(s): 大植孝治, 福澤正洋
  • Total Pages: 459-466
  • Publisher: 医薬ジャーナル社