Establishment of prognostic factor(s) by analysis of genetic abnormality and elucidation of the mechanism of drug resistance in nephroblastoma

2013 Fiscal Year Final Research Report

• Project/Area Number: 24791099
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Research Institute for Clinical Oncology, Saitama Cancer Center
• Principal Investigator: MASAYUKI Haruta 埼玉県立がんセンター(臨床腫瘍研究所), その他部局等, 研究員 (80392190)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: 腎芽腫 / 予後因子

Research Abstract

In nephroblastoma, identification of new prognostic markers for better therapy planning are needed to improve the mortality and recurrence rate, and prevent side and late effects. In this study, we examined genetic and epigenetic abnormalities of the 5 genes ( WT1, CTNNB1, WTX, TP53 and IGF2) and DNA methylation status of three tumor suppressor genes ( RASSF1A, DCR2 and CASP8) in Japanese nephroblastoma. WTX mutation and RASSF1A hypermethylation was correlated with poor prognosis by Kaplan-Meier analysis (p=0.040 and p=0.043, respectively). Nephroblastoma patients with both WTX and TP53 mutation particularly showed poor prognosis.

Research Products

• [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 Volume: (in press)
  • Peer Reviewed
• [Journal Article] RASSF1A methylation indicates a poor prognosis in hepatoblastoma patients (2013)
  • Author(s): Honda S, Miyagi H, Suzuki H, Minato M, Haruta M, Kaneko Y, Hatanaka KC, Hiyama E, Kamijo T, Okada T, Taketomi A
  • Journal Title: Pediatr Surg Int Volume: 29 Pages: 1147-52
  • DOI: 10.1007/s00383-013-3371-z
  • Peer Reviewed
• [Journal Article] Meiosis error and subsequent genetic and epigenetic alterations invoke the malignant transformation of germ cell tumor (2013)
  • Author(s): Ichikawa M, Arai Y, Haruta M, Furukawa S, Ariga T, Kajii T, and Kaneko Y
  • Journal Title: Genes Chromosomes Cancer Volume: 52 Pages: 274-86
  • DOI: 10.1002/gcc.22027
  • 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, Arai Y, Watanabe N, Fujiwara Y, Honda S, Ohshima J, Kasai F, Nakadate H, Horie H, Okita H, Hata JI, Fukuzawa M, Kaneko Y
  • Journal Title: Cancer Sci Volume: 103 Pages: 1129-35
  • DOI: 10.1111/j.1349-7006.2012.02269.x
  • Peer Reviewed
• [Journal Article] Methylation of the RASSF1A promoter is predictive of poor outcome among patients with Wilms tumor (2012)
  • Author(s): Ohshima J, Haruta M, Fujiwara Y, Watanabe N, Arai Y, Ariga T, Okita H, Koshinaga T, Oue T, Hinotsu S, Nakadate H, Horie H, Fukuzawa M, Kaneko Y
  • Journal Title: Pediatr Blood Cancer Volume: 59 Pages: 499-505
  • DOI: 10.1002/pbc.24093
  • Peer Reviewed
• [Presentation] WTX 遺伝子変異は腎芽腫の予後予測因子である (2012)
  • Author(s): 春田雅之, 他
  • 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: 20121130-1202
• [Presentation] WTX mutation is a new prognostic factor for Wilms tumor (2012)
  • Author(s): Haruta M, et. Al
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
  • Year and Date: 20120919-21
• [Remarks] 埼玉県立がんセンター 臨床腫瘍研究所
  • URL: http://www.saitama-cc.jp/rinsyousyuyoulabo/index.html