Comprehensive genome analyses of neuroblastoma

2010 Fiscal Year Final Research Report

• Project/Area Number: 20591269
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Chiba Cancer Center (Research Institute)
• Principal Investigator: OHIRA Miki Chiba Cancer Center (Research Institute), がんゲノムセンター・がんゲノム研究室, 室長 (20311384)
• Co-Investigator(Renkei-kenkyūsha): LI Yuanyuan 千葉県がんセンター(研究所), がん治療開発グループ・がん先進治療開発研究室, 特別研究員 (00392259) ; NAKAGAWARA Akira 千葉県がんセンター, センター長 (50117181)
• Project Period (FY): 2008 – 2010
• Keywords: 神経芽腫 / マイクロアレイ / 遺伝子 / ゲノム

Research Abstract

Neuroblastoma is a childhood tumor originating from progenitor cells of the sympathetic nervous system. The tumor displays a broad spectrum of clinical behavior, ranging from spontaneous regression to fatal progression despite intensive therapy. We have been collecting molecular signatures of each tumor subset, such as genomic copy number changes and mRNA expression profiles, to clarify molecular mechanism of oncogenesis and progression of neuroblastoma. In this study, we further conducted the analyses to find epigenetic changes occurred in aggressive neuroblastomas as well as miRNA expression profiling of the tumors.

Research Products

• [Journal Article] Global genomic and RNA profiles for novel risk stratification of neuroblastoma. (2010)
  • Author(s): Ohira M, Nakagawara A
  • Journal Title: Cancer Sci. Vol.101, No.11 Pages: 2295-2301
  • Peer Reviewed
• [Journal Article] Concordance for neuroblastoma in monozygotic twins : case report and review of the literature. (2010)
  • Author(s): Tajiri T, Souzaki R, Kinoshita Y, Tanaka S, Koga Y, Suminoe A, Hara T, Kohashi K, Oda Y, Masumoto K, Ohira M, Nakagawara A, Taguchi T
  • Journal Title: J Pediatr Surg Vol.45, No.12 Pages: 2312-2316
  • Peer Reviewed
• [Journal Article] Meta-analysis of neuroblastomas reveals a skewed ALK mutation spectrum in tumors with MYCN amplification. (2010)
  • Author(s): De Brouwer S, De Preter K, Kumps C, Zabrocki P, Porcu M, Westerhout EM, Lakeman A, Vandesompele J, Hoebeeck J, Van Maerken T, De Paepe A, Laureys G, Schulte JH, Schramm A, Van Den Broecke C, Vermeulen J, Van Roy N, Beiske K, Renard M, Noguera R, Delattre O, Janouiex-Lerosey I, Kogner P, Martinsson T, Nakagawara A, Ohira M, Caron H, Eggert A, Cools J, Versteeg R, Speleman F
  • Journal Title: Clin Cancer Res Vol.16, No.17 Pages: 4353-4362
  • Peer Reviewed
• [Journal Article] HDM2 impairs Noxa transcription and affects apoptotic cell death in a p53/p73-dependent manner in neuroblastoma. (2010)
  • Author(s): Shi Y, Takenobu H, Kurata K, Yamaguchi Y, Yanagisawa R, Ohira M, Koike K, Nakagawara A, Jiang LL, Kamijo T
  • Journal Title: Eur J Cancer Vol.46, No.12 Pages: 2324-2334
  • Peer Reviewed
• [Journal Article] Bmi1 is a MYCN target gene and regulates tumorigenesis via repression of KIF1Bβ and TSLC1 in neuroblastoma. (2010)
  • Author(s): Ochiai H, Takenobu H, Nakagawa A, Yamaguchi Y, Kimura M, Ohira M, Okimoto Y, Fujimura Y, koseki H, Kohno Y, Nakagawara A, Kamijo T
  • Journal Title: Oncogene Vol.29, No.18 Pages: 2681-2690
  • Peer Reviewed
• [Journal Article] Accurate outcome prediction in neuroblastoma across independent datasets using a multi-gene signature. (2010)
  • Author(s): De Preter K, Vermeulen J, Brors B, Delattre O, Eggert A, Fischer M, Janoueix-Lerosey I, Lavarino C, Maris J, Mora J, Nakagawara A, Oberthuer A, Ohira M, Schleiermacher G, Schramm A, Schute J, Wang Q, Westermann F, Speleman F, Vandesompele J
  • Journal Title: Clin Cancer Res Vol.16, No.5 Pages: 1532-1541
  • Peer Reviewed
• [Journal Article] Robust model selection for classification of microarrays. (2009)
  • Author(s): Suzuki I, Takenouchi T, Ohira M, Oba S, Ishii S
  • Journal Title: Cancer Inform Vol.7, No.25 Pages: 141-157
  • Peer Reviewed
• [Journal Article] High expression of ncRAN, a novel non-coding RNA mapped to 17q25.1, is associated with poor prognosis in neuroblastoma. (2009)
  • Author(s): Yu M, Ohira M, Li Y, Niizuma H, Oo ML, Zhu Y, Ozaki T, Isogai E, Kamijo T, Nakamura Y, Koda T, Oba S, Yu B, Nakagawara A
  • Journal Title: Int J Oncol Vol.34, No.4 Pages: 931-938
  • Peer Reviewed
• [Journal Article] Distinct role of ShcC docking protein in the differentiation of neuroblastoma. (2009)
  • Author(s): Miyake I, Ohira M, Nakagawara A, Sakai R
  • Journal Title: Oncogene Vol.28, No.5 Pages: 662-673
  • Peer Reviewed
• [Journal Article] Novel risk stratification of patients with neuroblastoma by genomic signature which is independent of molecular signature. (2008)
  • Author(s): Tomioka N, Oba S, Ohira M, Misra A, Fridlyand J, Ishii S, Nakamura Y, Isogai E, Hirata T, Yoshida Y, Todo S, Kaneko Y, Albertson D, Pinkel D, Feuerstein B, Nakagawara A
  • Journal Title: Oncogene Vol.27, No.4 Pages: 441-449
  • Peer Reviewed
• [Journal Article] A novel HECT-type E3 ubiquitin protein ligase NEDL1 enhances the p53-mediated apoptotic cell death in its catalytic activity-independent manner. (2008)
  • Author(s): Li Y, Ozaki T, Kikuchi H, Yamamoto H, Ohira M, Nakagawara A
  • Journal Title: Oncogene Vol.27, No.26 Pages: 3700-3709
  • Peer Reviewed
• [Journal Article] ERAP140/Nbla10993 is a novel favorable prognostic indicator for neuroblastoma induced in response to retinoic acid. (2008)
  • Author(s): Arai H, Ozaki T, Niizuma H, Nakamura Y, Ohira M, Takano K, Matsumoto M, Nakagawara A
  • Journal Title: Oncology Rep, Vol.19, No.6 Pages: 1381-1388
  • Peer Reviewed
• [Journal Article] Loss of imprinting of IGF2 correlates with hypermethylation of the H19 differentially methylated region in hepatoblastoma. (2008)
  • Author(s): Honda S, Arai Y, Haruta M, Sasaki F, Ohira M, Yamaoka H, Horie H, Nakagawara A, Hiyama E, Todo S, Kaneko Y
  • Journal Title: Br J Cancer Vol.99, No.11 Pages: 1891-1899
  • Peer Reviewed
• [Journal Article] Expression of TSLC1, a candidate tumor suppressor gene mapped to chromosome 11q23, is down-regulated in unfavorable neuroblastoma without promoter hypermethylation. (2008)
  • Author(s): Ando K, Ohira M, Ozaki T, Nakagawa A, Akazawa K, Suenaga Y, Nakamura Y, Koda T, Kamijo T, Murakami Y, Nakagawara A
  • Journal Title: Int J Cancer Vol.123, No.9 Pages: 2087-2094
  • Peer Reviewed
• [Journal Article] N-MYC promotes cell proliferation through a direct transactivation of neuronal leucine-rich repeat protein-1 (NLRR1) gene in neuroblastoma. (2008)
  • Author(s): Hossain S, Ozaki T, Wang H, Nakagawa A, Takenobu H, Ohira M, Kamijo T, Nakagawara A
  • Journal Title: Oncogene Vol.27, No.46 Pages: 6075-6082
  • Peer Reviewed
• [Journal Article] KIF1Bbeta functions as a haploidinsufficient tumor suppressor gene mapped to chromosome 1p36.2 by inducing apoptotic cell death. (2008)
  • Author(s): Munirajan AK, Ando K, Mukai A, Takahashi M, Suenaga Y, Ohira M, Koda T, Hirota T, Ozaki T, Nakagawara A
  • Journal Title: J Biol Chem Vol.283, No.36 Pages: 24426-24434
  • Peer Reviewed
• [Journal Article] Novel oncogenic mutations of ALK kinase in neuroblastoma. (2008)
  • Author(s): Chen Y, Takita J, Choi YL, Kato M, Ohira M, Sanada M, Wang L, Soda M, Kikuchi A, Igarashi T, Nakagawara A, Hayashi Y, Mano H, Ogawa A
  • Journal Title: Nature Vol.455, No.7215 Pages: 971-974
  • Peer Reviewed
• [Journal Article] Plasma midkine level is a prognostic factor for human neuroblastoma. (2008)
  • Author(s): Ikematsu S, Nakagawara A, Nakamura Y, Ohira M, Shinjo M, Kishida S, Kadomatsu K
  • Journal Title: Cancer Sci Vol.99, No.10 Pages: 2070-2074
  • Peer Reviewed
• [Journal Article] Identification of genes targeted by CpG island methylator phenotype in neuroblastomas, and their possible integrative involvement in poor prognosis. (2008)
  • Author(s): Abe M, Watanabe N, McDonell N, Takato T,Ohira M, Nakagawara A, Ushijima T
  • Journal Title: Oncology Vol.74, No.1-2 Pages: 50-60
  • Peer Reviewed
• [Presentation] 神経芽腫のカスタム化遺伝子発現ミニチップのclinical validationと腫瘍リスク分類構築における意義の検討 (2010)
  • Author(s): 大平美紀, 他
  • Organizer: 第52回日本小児血液学会総会・第26回日本小児がん学会学術集会合同開催
  • Place of Presentation: 大阪
  • Year and Date: 2010-12-18
• [Presentation] Genomic and expression profiles specifically characterize therapy-resistant aggressive neuroblastomas. (2010)
  • Author(s): 大平美紀, 他
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-23
• [Presentation] Risk stratification of neuroblastoma by genomic signature including ALK abnormality. (2010)
  • Author(s): 大平美紀, 他
  • Organizer: 国際神経芽腫学会2010(ANR2010)
  • Place of Presentation: スウェーデン・ストックホルム
  • Year and Date: 2010-06-24
• [Presentation] Clinical application of genomic signature including ALK mutation to the new tumor risk classification for neuroblastoma. (2010)
  • Author(s): 大平美紀, 他
  • Organizer: 米国癌学会総会(AACR)2010
  • Place of Presentation: 米国・ワシントンDC
  • Year and Date: 2010-04-18
• [Presentation] ゲノム異常パターンに基づく神経芽腫の新規リスク分類の構築-ALK遺伝子異常とゲノムコピー数異常の統合解析 (2009)
  • Author(s): 大平美紀, 他
  • Organizer: 第51回日本小児血液学会総会・第25回日本小児がん学会学術集会合同開催
  • Place of Presentation: 千葉・舞浜
  • Year and Date: 2009-11-27
• [Presentation] Clinical application of genomic signature including ALK mutation to the new tumor risk classification system for neuroblastoma. (2009)
  • Author(s): 大平美紀, 他
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-02
• [Presentation] 遺伝子発現プロファイルに基づく神経芽腫の予後予測ミニチップシステム (2009)
  • Author(s): 大平美紀, 他
  • Organizer: 日本人類遺伝学会第54回大会
  • Place of Presentation: 東京・品川
  • Year and Date: 2009-09-26
• [Presentation] マイクロアレイに基づく神経芽腫のリスク分類システムの構築 (2009)
  • Author(s): 大平美紀, 他
  • Organizer: 第16回日本遺伝子診療学会
  • Place of Presentation: 札幌
  • Year and Date: 2009-08-01
• [Presentation] High expression of ncRAN, a long non-coding RNA mapped to 17q25, is associated with aggressiveness and poor prognosis of neuroblastoma. (2009)
  • Author(s): 大平美紀, 他
  • Organizer: 米国癌学会総会(AACR)2009
  • Place of Presentation: 米国・デンバー
  • Year and Date: 2009-04-20
• [Presentation] Integrated analysis of genome copy number aberrations and its application for risk stratification for neuroblastoma. (2008)
  • Author(s): 大平美紀, 他
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-29
• [Presentation] Practical application and validation of a customized expression microarray-based diagnostic system toward the new risk classification of neuroblastoma. (2008)
  • Author(s): 大平美紀, 他
  • Organizer: 第13回国際神経芽腫学会 Advances in Neuroblastoma Research (ANR)2008
  • Place of Presentation: 千葉・幕張
  • Year and Date: 2008-05-23