2023 Fiscal Year Final Research Report
Extensive genetic analysis of nodal cytotoxic T-cell lymphoma
| Project/Area Number |
21K06920
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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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| Review Section |
Basic Section 49020:Human pathology-related
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| Research Institution | Fujita Health University (2022-2023)
Aichi Cancer Center Research Institute (2021) |
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Principal Investigator |
Kato Seiichi 藤田医科大学, 医学部, 教授 (30584669)
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| Co-Investigator(Kenkyū-buntansha) |
奥野 友介 名古屋市立大学, 医薬学総合研究院(医学), 教授 (00725533)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | EBV陽性節性末梢性T細胞リンパ腫 / clonal hematopoiesis / RHOA G17V / EBV genome |
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| Outline of Final Research Achievements |
EBV+ nodal T- and NK-cell lymphoma (EBV+ nPTCL) is a T-cell lymphoma that presents as a primary nodal disease with T-cell phenotype and EBV harboring on tumor cells. In this study, whole-exome and/or genome sequencing was performed on 22 cases of EBV+ nPTCL. TET2 (68%) and DNMT3A (32%) were observed to be the most frequently mutated genes. The RHOA G17V mutation was identified in two patients. In four patients with TET2/DNMT3A alterations, bone marrow [BM] or spleen were available as paired normal samples. Three out of these four cases had at least one identical TET2/DNMT3A mutation in the BM or spleen. Additionally, the whole part of the EBV genome was sequenced and structural variations were found frequent among the EBV genomes (63%). Overall, the frequent TET2 and DNMT3A mutations in EBV+ nPTCL seem to be closely associated with clonal hematopoiesis and, together with the EBV genome deletions, may contribute to the pathogenesis of this intractable lymphoma.
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| Free Research Field |
人体病理学
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| Academic Significance and Societal Importance of the Research Achievements |
EBV陽性節性末梢性T細胞リンパ腫（EBV+ nPTCL）はアジアからの報告が多い予後不良な疾患であるがその分子病態についてほとんど解明されておらず、標準治療もない。本研究では、多くのEBV+ nPTCL症例ににおいてclonal hematopoiesisが背景にある可能性が高く、またEBVゲノム欠失が高頻度に見られ、腫瘍進展に寄与していることが示唆された。また1症例のみであるが、腫瘍細胞中のEBVゲノムにヒトゲノムが組み込まれており、PD-L1高発現に寄与している症例もあった。このように本研究はEBV+ nPTCLの分子病態の一端を明らかにした。
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