Development of methodology detecting immunoglobulin related fusion genes in pediatric leukemia

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K17384
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: National Center for Child Health and Development
• Principal Investigator: Watanabe Satoru 国立研究開発法人国立成育医療研究センター, 小児血液・腫瘍研究部, 研究員 (00829418)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 小児がん / 白血病 / リンパ腫

Outline of Final Research Achievements

We designed and modified a custom panel for the immunoglobulin (IG) region and performed RNA panel sequencing analysis on pediatric hematopoietic tumors suspected of IGH-DUX4 or IGH-MYC based on flow cytometry and FISH analysis. IGH-DUX4 was detected in 8 of 10 cases and IGH-MYC in 2 of 3 cases, and the fusion points were confirmed by direct sequencing.
In this study, we succeeded in creating a custom panel that can generally detect fusion genes containing the IG region. We plan to use this panel to detect novel fusion genes and search for therapeutic target genes in cases with Acute Lymphoblastic leukemia/lymphoma, and mature B cell leukemia/lymphoma for which fusion genes have not yet been identified.

Free Research Field

血液腫瘍

Academic Significance and Societal Importance of the Research Achievements

近年、小児急性リンパ芽球性白血病(ALL)に対する次世代シーケンス等の解析が進み、IGH-DUX4やIGH-EPOR等の免疫グロブリン(IG)が関連する遺伝子再構成がB前駆細胞型ALLの5-10%で同定され、新規の予後因子候補と期待されているが実臨床での検出方法は未だに確立されていないが、本研究でIG領域を含む融合遺伝子を検出可能なカスタムパネルを作製することに成功した。
今後はこのパネルを用いて解析を行うことにより新規の融合遺伝子や治療標的の候補となる遺伝子異常を同定し、治療の層別化に利用することで、小児ALLの予後の向上に役立てられると考えている。