2018 Fiscal Year Final Research Report
Molecular cytogenetic studies of MYC and PVT1 rearrangements in refractory and relapsed lymphoma
| Project/Area Number |
16K09856
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
Taniwaki Masafumi 京都府立医科大学, 医学(系)研究科(研究院), 特任教授 (80163640)
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| Co-Investigator(Kenkyū-buntansha) |
名越 久朗 京都府立医科大学, 医学部附属病院, 研究員 (80713924)
知念 良顕 京都府立医科大学, 医学(系)研究科(研究院), 助教 (10757602)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | 難治性リンパ腫 / 8q24染色体異常 / キメラmRNA / PVT1 / long noncoding RNA / 遺伝子増幅 |
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| Outline of Final Research Achievements |
We have detected alteration of long noncoding RNA (lncRNA) PVT1 gene in two diffuse large B-cell lymphoma cell lines; chimeric gene in one and high-magnitude amplification in the other. Fluorescence in situ hybridization (FISH) using own two original FISH probes, PVT1-adjacent (PVT1-A) and PVT1-spanning (PVT1-S), demonstrated a breakpoint of the chimeric gene around exons 1-2 of PVT1. RNAseq analysis identified this chimeric gene as PVT1-ELK2AP. High-magnitude amplification of PVT1 gene was found on homogeneously staining region at the derivative chromosome 8 as detected by FISH with PVT1-S probe. The amplicon harbored both MYC and PVT1 gene, the size of which was 1.4Mb. The current study suggests that chimeric formation and amplification of lncRNA PVT1 gene may contribute to the pathophysiology and the molecular mechanism of refractoriness to treatment in diffuse large B-cell lymphoma.
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| Free Research Field |
血液腫瘍
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| Academic Significance and Societal Importance of the Research Achievements |
非ホジキンリンパ腫の難治性に関与する新規分子異常が同定できれば，診断や適切な治療法選択の指標と応用できる．そのためには，PVT1キメラをゲノムやmRNAレベルで迅速に検出する臨床検査法の確立が重要であり，PCRやFISHによって日常診療への導入が促進される．さらに，新規分子異常が同定は新規治療薬の開発にも寄与する．新規分子異常に基づいた層別化あるいはリスク分類を確立し，適切な治療戦略が立案できれば，難治性であるがゆえの過剰治療を回避することが可能である．人口構成が高齢化するなか非ホジキンリンパ腫の罹患率は上昇しているため，本研究の社会的ならびに医療経済的なインパクトは大きいと考えられる．
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