GENMOME-WIDEANALYSIS OF GENETIC BASIS OF HEMATOLOGICAL MALIGNANCIES

2007 Fiscal Year Final Research Report Summary

• Project/Area Number: 18390279
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: The University of Tokyo
• Principal Investigator: OGAWA SEISHI The University of Tokyo, HOSPITAL, ASSOCIATED PROFESSOR (60292900)
• Co-Investigator(Kenkyū-buntansha): KUMANO Keiki The University of Tokyo, HOSPITAL, ASSOCIATED PROFESSOR (90396721) ; HANGAISHI Akira The University of Tokyo, HOSPITAL, ASSISTANT PROFESSOR (20344450) ; ASAI Takashi The University of Tokyo, HOSPITAL, ASSISTANT PROFESSOR (10376436)
• Project Period (FY): 2006 – 2007
• Keywords: CANCER / GENETICS / ALLELIC IMBALANCES / MICROARRAY / LEUKEMIA

Research Abstract

The purpose of this project is to explore the genetic basis of hematopoietic malignancies through genome-wide analysis of genetic lesions in a variety of blood cancers, using SNP genotyping microarrays. We performed SNP array analysis of more than 1500 blood cell cancers including acute leukemia usand lymphoma in 2006, and interrogating the target genetic lesions in these cancers based on the SNP array data. A number of candidate lesions have been identified though the analysis. For example, through the analysis of 399 pediatric ALL, we identified novel fusion genes in which PAX5 is a common fusion partner We found that PAX5, an essential transcription factor in B cell development, is fused with a variety of partner genes and that the fusion products inhibit normal functions of PAX5 in a dominant negative fashion. On the other hand, through the analysis of 171 MDS samples, we showed that about 30% of MDS cases have copy number neutral LOB which preferentially involves particular genomic loci. Furthermore, we identified a novel target of MDS, mds11, which are tightly associated with 11qUP'D. It was mutated〜6% of MDS and the mutant mds11 strongly transform 3T3 fibroblase in vitro in a dominant manner We also disclosed other targets or candidates of targets from non-Hodgikin lymphoma and adult T Dell leukemia, which are currently under investigation.

Research Products

• [Journal Article] Molecular allelokaryotyping of pediatric acute lymphoblastic leukemias by high-resolution single nucleotide polymorphism oligonucleotide genomic microarray (2008)
  • Author(s): Kawamata N, et, al.
  • Journal Title: Blood 111 Pages: 776-784
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Method bW5-206 (2008)
  • Author(s): Ogawa S, el. al.
  • Journal Title: Molecular Biology 369Comparative Genomics Volume2, Humana Press (Editor Nicholas Bergman H) Pages: 185-206
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Molecular allelokaryotyping of pediatric acute lymphoblastic leukemias by high-resolution single nucleotide polymorphism oligonucleotide genomic microarray (2008)
  • Author(s): Kawamata N, Ogawa S, Zimmermann M, Kato M, Sanada M, Hemminki K, Yamatomo G, Nannya Y, Koehler R, Flohr T, Miller CW, Harbott J, Ludwig WD, Stanulla M, Schrappe M, Bartram CR, Koeffler HP
  • Journal Title: Blood. 111 Pages: 776-784
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Highly sensitive method for genomewide detection of allelic composition in nonpaired, primary tumor specimens by use of affymetrix single-nucleotide-polymorphism genotyping microarrays (2007)
  • Author(s): Yamamoto G, et. al.
  • Journal Title: American Journal of Human Genetics 81 Pages: 114-26
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Expression profiling of immature thymocytes revealed a novel homeobox gene that regulates double-negative thymocyte development (2007)
  • Author(s): Kawazu M, el. al.
  • Journal Title: Journal of Immunology 179 Pages: 5335-5345
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Evaluation of genome-wide power of genetic association studies based on empirical data from the HapMap project (2007)
  • Author(s): Nannya Y, et, al.
  • Journal Title: Human Molecular Genetics 16 Pages: 3494-505
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] sensitive method for genomewide detection of allelic composition in nonpaired, primary tumor specimens by use of affymetrix single-nucleotide-polymorphism genotyping microarrays (2007)
  • Author(s): Yamamoto G, Nannya Y, Kato M, Sanada M, Levine RL, Kawamata N, Hangaishi A, Kurokawa M, Chiba S, Gilliland DG, Koeffler HP, Ogawa S. Highly
  • Journal Title: Am J Hum Genet. 81 Pages: 114-126
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Expression profiling of immature thymocytes revealed a novel homeobox gene that regulates double-negative thymocyte development (2007)
  • Author(s): Kawazu M, Yamamoto G, Yoshimi. M, Yamamoto K, Asai T, Ichikawa M, Seo S, Nakagawa M, Chiba S, Kurokawa M, Ogawa S
  • Journal Title: J Immunol. 179 Pages: 5335-5345
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Evaluation of genome-wide power of genetic association studies based on empirical data from the HapMap project (2007)
  • Author(s): Nannya Y, Taura K, Kurokawa M, Chiba S, Ogawa S
  • Journal Title: Hum Mol Genet. 16 Pages: 3494-3505
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] SNP Chip Analysis of Myelodysplastic Syndromes Disclosed High Frequency of Uniparental Disomy and a Novel Dominant Mutation as the Target of llq UPD. (2007)
  • Author(s): Sanada M, et. al.
  • Organizer: The 49th Annual Meeting of American Siciety of Hematology
  • Place of Presentation: 米国アトランタ
  • Year and Date: 2007-12-11
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] SNP chip analysis of myelodysplastic syndromes disclosed High Frequency of uniparental disomy and a novel dominant mutation as the target of 11qUPD
  • Author(s): Sanada M, Lee-Y., Shih L, Suzuki T, Yamamoto G, Nannya Y, Yanagimoto-Sakata M, Kato M, Kumano K, Kawamata N, Mori H, Kurokawa M, Chiba S, Omine M, Koeffler PH, S Ogawa
  • Description: 「研究成果報告書概要(欧文)」より
• [Remarks] 「研究成果報告書概要(和文)」より
  • URL: http://www.genome.umin.ac.jp