2005 Fiscal Year Final Research Report Summary
Exploring leukemogenic mechanism using genomic analysis and mouse genetics.
| Project/Area Number |
16390272
|
|---|
| 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, Faculty of Medicine, Visiting Assistant Professor, 医学部附属病院, 寄附講座教員 (60292900)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
CHIBA Shigeru The University of Tokyo, Faculty of Medicine, Assistant Professor, 医学部附属病院, 助教授 (60212049)
SUZUKI Takahiro The University of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 寄附講座教員 (40345210)
KUMANO Keiki The University of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 研究拠点形成特任研究員 (90396721)
IZUTSU Koji The University of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (30361471)
YAMAMOTO Go The University of Tokyo, Faculty of Medicine, Medical Staff, 医学部附属病院, 医員 (70396753)
|
|---|
| Project Period (FY) |
2004 – 2005
|
| Keywords | Leukemia / Copy number analysis / SNP array / CNAG / Allele-specific analysis / UPD / LOH |
|---|
| Research Abstract |
Leukemia is a neoplastic state in which deregulated cell division, differentiaion, and apoptosis lead to unregulated clonal proliferation of hematopoietic progenitors and the molecular basis for these abnormalities should be finally ascribed to the genetic alterations in leukemia genome. Thus the identification of those genetic changes is of crucial importance for the understanding of leukemogeneic mechanism. The purpose of this study is exploring leukemia genomes for genetic abnormalities using advanced microarray technologies, identifying their molecular targets and clarifying the leukemogenic mechanism through analysis of the target molecules using mouse genetics. In this study, we newly developed a robust system for copy number detection of cancer genome using high-density oligonucleotide microarrays (CNAG) and comprehensively analyzed copy number alterations in leukemia genomes. We analyzed a total of 886 leukemia samples and found numerous copy number abnormalities, including those that are commonly involved in multiple samples. Due to the extremely high resolution, the candidate gene that might be relevant to leukemogenesis was uniquely identified for many abnormal regions. Blimp1 is one of such target found in a homozygous deletion at 6q21 in ATL. Interestingly, conditional Blimp1 targeted mice show lymphonode swelling as well as splenomegaly. In addition, we revealed that it is mutated in primary ATL samples and when expressed in Hela cells, induces cell arrest at both G1 and G2 phases, indicating its tumor suppressive function.
|
Research Products
(12 results)
-
-
-
-
-
-
-
[Journal Article] A robust algorithm for copy number detection using high-density oligonucleotide single nucleotide polymorphism genotyping arrays.2005
Author(s)
Nannya Y, Sanada M, Nakazaki K, Hosoya N, Wang L, Hangaishi A, Kurokawa M, Chiba S, Bailey DK, Kennedy GC, Ogagwa S.
-
Journal Title
Cancer Res. 65
Pages: 6071-6079
Description
「研究成果報告書概要(欧文)」より
-
[Journal Article] Identification of a SRC-like tyrosine kinase gene, FRK, fused with ETV6 in a patient with acute myelogenous leukemia carrying a t(6;12)(q21;p13) translocation.2005
Author(s)
Hosoya N, Qiao Y, Hangaishi A, Wang L, Nannya Y, Sanada M, Kurokawa M, Chiba S, Hirai H, Oagwa S.
-
Journal Title
Genes Chromosomes Cancer 42
Pages: 269-279
Description
「研究成果報告書概要(欧文)」より
-
-
[Journal Article] Functional Domains of Runx1 Are Differentially Required for CD4 Repression, TCR{beta} Expression, CD4/8 Double-Negative to CD4/8 Double-Positive Transition in Thymocyte Development.2005
Author(s)
Kawazu M, Asai T, Ichikawa M, Yamamoto G, Saito T, Goyama S, Mitani K, Miyazono K, Chiba S, Ogawa S, Kurokawa M, Hirai H.
-
Journal Title
J.Immunol. 174
Pages: 3526-3533
Description
「研究成果報告書概要(欧文)」より
-
-
