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Exploring new gene target of 4q-UPD in Myelodysplastic syndromes

Research Project

Project/Area Number 21790907
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Hematology
Research InstitutionThe University of Tokyo

Principal Investigator

SANADA Masashi  The University of Tokyo, 医学部附属病院, 特任助教 (20529044)

Project Period (FY) 2009 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2009: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywords骨髄異形成症候群 / ゲノム / 遺伝子変異 / LOH
Research Abstract

Using high resolution single nucleotide polymorphism (SNP) microarrays to examine DNA copy number alterations and loss of heterozygosity (LOH), copy-number neutral LOH (aUPD) were seen in about 30% cases of MDS. We identified recurring aUPD involving 4q24 and led to the identification of TET2 mutations by target sequencing. We also conducted whole exome analysis of 20 MDS samples, where entire exon sequences were enriched by using SureSelect Human All Exon kit and were subjected to resequencing analysis using Genome Analizer IIx. By comparing sequences in tumors and paired T cells, nearly 200 somatic mutations and 10 insertions-deletions were detected in total. Our results suggested that target-capture resequencing technology is a powerful method to identify new gene mutations that are implicated in the pathogenesis of MDS.

Report

(3 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • Research Products

    (44 results)

All 2011 2010 2009

All Journal Article (24 results) (of which Peer Reviewed: 24 results) Presentation (16 results) Book (4 results)

  • [Journal Article] IDH1 and IDH2 mutations are rare in pediatric myeloid malignancies.2011

    • Author(s)
      Oki K, Takita J, Hiwatari M, Nishimura R, Sanada M, 他7名
    • Journal Title

      Leukemia. 25(2)

      Pages: 382-384

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Oncogenic mutations of ALK in neuroblastoma.2011

    • Author(s)
      Ogawa S, Takita J, Sanada M, Hayashi Y.
    • Journal Title

      Cancer Sci. 102(2)

      Pages: 302-308

    • NAID

      10029289653

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] A nonsense mutation of IDH1 in myelodysplastic syndromes and related disorders.2011

    • Author(s)
      Yoshida K, Sanada M, Kato M, 他7名
    • Journal Title

      Leukemia. 25(1)

      Pages: 184-186

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] A nonsense mutation of IDH1 in myelodysplastic syndromes and related disorders.2011

    • Author(s)
      Yoshida K, et al.
    • Journal Title

      Leukemia

      Volume: 102 Pages: 184-186

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] IDH1 and IDH2 mutations are rare in pediatric myeloid malignancies.2011

    • Author(s)
      Oki K., et al
    • Journal Title

      Leukemia

      Volume: 25 Pages: 382-384

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Deregulated intracellular signaling by mutated c-CBL in myeloid neoplasms.2010

    • Author(s)
      Ogawa S, Shih LY, Suzuki T, 他3名, Sanada M.
    • Journal Title

      Clin Cancer Res. 16(15)

      Pages: 3825-3831

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Genomic profiling of adult acute lymphoblastic leukemia (ALL) by single nucleotide polymorphism oligonucleotide microarray and comparison to pediatric ALL.2010

    • Author(s)
      Okamoto R, Ogawa S, Nowak D, 他3名, Sanada M, 他6名
    • Journal Title

      Haematologica 95(9)

      Pages: 1481-1488

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Prognostic significance of genetic alterations detected by high-density single nucleotide polymorphism array in gastric cancer.2010

    • Author(s)
      Tada M, Kanai F, Tanaka Y, Sanada M, 他10名
    • Journal Title

      Cancer Sci. 101(5)

      Pages: 1261-1269

    • NAID

      10026592643

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] CBL mutations in juvenile myelomonocytic leukemia,but not in pediatric myelodysplastic syndrome.2010

    • Author(s)
      Shiba N, Kato M, Park MJ, Sanada M, 他6名
    • Journal Title

      Leukemia 24(5)

      Pages: 1090-1092

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Gain-of-function c-CBL mutations associated with uniparental disomy of 11q in myeloid neoplasms.2010

    • Author(s)
      Ogawa S, Sanada M, Shih L, 他4名
    • Journal Title

      Cell Cycle 9(6)

      Pages: 23-23

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Prevalence and prognostic impact of allelic imbalances associated with leukemic transformation of Philadelphia chromosome-negative myeloproliferative neoplasms.2010

    • Author(s)
      Thoennissen NH, Krug UO, 他8名, Sanada M, 他10名
    • Journal Title

      Blood. 115(14)

      Pages: 2882-2890

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Gain-of-function c-CBL mutations associated with uniparental disomy of 11q in myeloid neoplasms.2010

    • Author(s)
      Ogawa S, et al.
    • Journal Title

      Cell Cycle

      Volume: 23 Pages: 1051-1056

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Deregulated intracellular signaling by mutated c-CBL in myeloid neoplasms.2010

    • Author(s)
      Ogawa S, et al.
    • Journal Title

      Clinical Cancer Research

      Volume: 16 Pages: 3825-3831

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CBL mutations in juvenile myelomonocytic leukemia and pediatric myelodysplastic syndrome.2010

    • Author(s)
      Shiba N., et al.
    • Journal Title

      Leukemia

      Volume: 24 Pages: 1090-1092

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prevalence and prognostic impact of allelic imbalances associated with leukemic transformation of Philadelphia chromosome-negative myeloproliferative neoplasms.2010

    • Author(s)
      Thoennissen NH., et al
    • Journal Title

      Blood

      Volume: 115 Pages: 2882-2890

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Gain-of-function of mutated C-CBL tumour suppressor in myeloid neoplasms.2009

    • Author(s)
      Sanada M, Suzuki T, Shih LY, 他26名
    • Journal Title

      Nature. 460

      Pages: 904-908

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Frequent inactivation of A20 in B-cell lymphomas.2009

    • Author(s)
      Kato M, Sanada M, Kato I, 他26名
    • Journal Title

      Nature. 459

      Pages: 712-716

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] High-resolution genomic copy number profiling of glioblastoma multiforme by single nucleotide polymorphism DNA microarray.2009

    • Author(s)
      Yin D, Ogawa S,他8名, Sanada M, 他4名
    • Journal Title

      Mol Cancer Res. 7

      Pages: 665-677

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Gain-of-function mutations and copy number increases of Notch2 in diffuse large B-cell lymphoma.2009

    • Author(s)
      Lee SY, Kumano K, Nakazaki K, Sanada M, 他15名
    • Journal Title

      Cancer Sci. 100

      Pages: 920-926

    • NAID

      10025145854

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Single nucleotide polymorphism genomic arrays analysis of t(8;21) acute myeloid leukemia cells.2009

    • Author(s)
      Akagi T, Shih LY, 他6名, Sanada M, 他8名
    • Journal Title

      Haematologica. 94

      Pages: 1301-1306

    • NAID

      120001643240

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Hidden abnormalities and novel classification of t(15;17) acute promyelocytic leukemia (APL) based on genomic alterations.2009

    • Author(s)
      Akagi T, Shih LY, 他3名, Sanada M, 他5名
    • Journal Title

      Blood. 113

      Pages: 1741-1748

    • NAID

      120001249804

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Frequent genomic abnormalities in acute myeloid leukemia/myelodysplastic syndrome with normal karyotype.2009

    • Author(s)
      Akagi T, Ogawa S, 他4名, Sanada M, 他6名
    • Journal Title

      Haematologica. 94

      Pages: 213-223

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Molecular cloning of t(2;7)(p24.3;p14.2), a novel chromosomal translocation in myelodysplastic syndrome-derived acute myeloid leukemia.2009

    • Author(s)
      Fujita K, Sanada M, Harada H, 他5名
    • Journal Title

      J Hum Genet. 54

      Pages: 355-359

    • NAID

      10030730783

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Gain-of-function of mutated C-CBL tumour suppressor in myeloid neoplasms2009

    • Author(s)
      Sanada M, et al.
    • Journal Title

      Nature 460

      Pages: 904-908

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] 骨髄異形成症候群の全エクソン・シークエンス2010

    • Author(s)
      真田昌, ら
    • Organizer
      第72回日本血液学会学術集会
    • Place of Presentation
      横浜
    • Year and Date
      2010-09-26
    • Related Report
      2010 Annual Research Report
  • [Presentation] 骨髄系腫瘍におけるCBL変異の機能解析2010

    • Author(s)
      真田昌, ら
    • Organizer
      第72回日本血液学会学術集会
    • Place of Presentation
      横浜
    • Year and Date
      2010-09-25
    • Related Report
      2010 Annual Research Report
  • [Presentation] Genetic Basis of Myelodysplastic Syndromes2010

    • Author(s)
      真田昌
    • Organizer
      第69回日本癌学会学術総会
    • Place of Presentation
      大阪 リーガロイヤルホテル
    • Year and Date
      2010-09-23
    • Related Report
      2010 Annual Research Report
  • [Presentation] Molecular mechanisms of mutant C-CBL in myeloid neoplasms2010

    • Author(s)
      真田昌, ら
    • Organizer
      第69回日本癌学会学術総会
    • Place of Presentation
      大阪
    • Year and Date
      2010-09-22
    • Related Report
      2010 Annual Research Report
  • [Presentation] Molecular mechanisms of mutant C-CBL in myeloid neoplasms2010

    • Author(s)
      真田昌
    • Organizer
      15th Congress of the European Hematology Association
    • Place of Presentation
      バルセロナ(スペイン)
    • Year and Date
      2010-06-11
    • Related Report
      2010 Annual Research Report
  • [Presentation] 骨髄異形成症候群の全エクソンシークエンス2010

    • Author(s)
      真田昌, ら
    • Organizer
      第72回日本血液学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2010 Final Research Report
  • [Presentation] 骨髄系腫瘍におけるCBL変異の機能解析2010

    • Author(s)
      真田昌, ら
    • Organizer
      第72回日本血液学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2010 Final Research Report
  • [Presentation] Molecular mechanism of mutant C-CBL in myeloid neoplasms.2010

    • Author(s)
      真田昌, ら
    • Organizer
      第69回日本癌学会学術総会
    • Place of Presentation
      大阪
    • Related Report
      2010 Final Research Report
  • [Presentation] Genetic Basis of Myelody splastic syndromes2010

    • Author(s)
      真田昌
    • Organizer
      第69回日本癌学会学術総会
    • Place of Presentation
      大阪(招待講演)
    • Related Report
      2010 Final Research Report
  • [Presentation] Molecular mechanism of mutant C-CBL in myeloid neoplasms.2010

    • Author(s)
      真田昌
    • Organizer
      15th Congress of the European Hematology Association.
    • Place of Presentation
      バルセロナ、スペイン
    • Related Report
      2010 Final Research Report
  • [Presentation] Unique Gain-of-Function of Mutated c-CBL Tumor Suppresor in Myeloid Neoplasms2009

    • Author(s)
      真田昌
    • Organizer
      51th Annual Meeting of American Society of Hematology
    • Place of Presentation
      New Orleans, USA
    • Year and Date
      2009-12-07
    • Related Report
      2009 Annual Research Report
  • [Presentation] Gain-of-function mutations of C-CBL in Myeloid Neoplasms2009

    • Author(s)
      真田昌, ら
    • Organizer
      51th Annual Meeting of the American Society of Hematology
    • Place of Presentation
      オーランド、アメリカ
    • Related Report
      2010 Final Research Report
  • [Presentation] 11番染色体長腕UPDを有する骨髄異形成症候群におけるがん抑制遺伝子c-cblの機能獲得型変異2009

    • Author(s)
      真田昌, ら
    • Organizer
      第71回日本血液学会学術総会
    • Place of Presentation
      京都
    • Related Report
      2010 Final Research Report
  • [Presentation] Gain-of-function of mutated c-Cbl tumor suppressor associated with 11q UPD in myeloid neoplasms2009

    • Author(s)
      真田昌, ら
    • Organizer
      第68回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2010 Final Research Report
  • [Presentation] 骨髄異形成症候群における11番染色体長腕UPDとがん抑制遺伝子c-Cblの機能獲得型変異2009

    • Author(s)
      真田昌, ら
    • Organizer
      日本人類遺伝学会第54回大会
    • Place of Presentation
      東京
    • Related Report
      2010 Final Research Report
  • [Presentation] Gain-of-function mutations of c-Cbl tumor suppressor in MDS and MDS/MPD associated with 11q UPD.2009

    • Author(s)
      真田昌, ら
    • Organizer
      16th Congress of the European Hematology Association.
    • Place of Presentation
      ベルリン、ドイツ
    • Related Report
      2010 Final Research Report
  • [Book] Annual Review 血液 20112011

    • Author(s)
      真田昌(共著)
    • Total Pages
      229
    • Publisher
      中外医学社
    • Related Report
      2010 Final Research Report
  • [Book] Annual Review血液20112011

    • Author(s)
      真田昌(共著)
    • Publisher
      中外医学社
    • Related Report
      2010 Annual Research Report
  • [Book] 血液診療エキスパート「貧血」2010

    • Author(s)
      真田昌(共著)
    • Total Pages
      253
    • Publisher
      中外医学社
    • Related Report
      2010 Final Research Report
  • [Book] 臨床に直結する血液疾患診療のエビデンス2009

    • Author(s)
      真田昌(共著)
    • Total Pages
      397
    • Publisher
      文光堂
    • Related Report
      2010 Final Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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