EBV+ nodal T/NK-cell lymphoma associated with clonal hematopoiesis and structural variations of the viral genome
Copyright © 2024 American Society of Hematology..
Epstein-Barr virus (EBV)+ nodal T- and NK-cell lymphoma (EBV+ nPTCL) is a peripheral T-cell lymphoma (PTCL) that presents as a primary nodal disease with T-cell phenotype and EBV harboring on tumor cells. To date, the genetic aspect of EBV+ nPTCL has not been fully investigated. 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 whose presence was associated with poor overall survival (p = 0.004). The RHOA p.Gly17Val mutation was identified in two patients who had TET2 and/or DNMT3A mutations. In four patients with TET2/DNMT3A alterations, blood cell-rich tissues (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 (SVs) were found frequent among the EBV genomes (63%). The most frequently identified type of SV was deletion. In one patient, four pieces of human chromosome 9, including PD-L1 were identified to be tandemly incorporated into the EBV genome. The 3'-untranslated region of PD-L1 was truncated, causing a high-level of PD-L1 protein expression. 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
Blood advances - (2024) vom: 01. März |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kato, Seiichi [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Revised 01.03.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1182/bloodadvances.2023012019 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369189590 |
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| 245 | 1 | 0 | |a EBV+ nodal T/NK-cell lymphoma associated with clonal hematopoiesis and structural variations of the viral genome |
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| 520 | |a Copyright © 2024 American Society of Hematology. | ||
| 520 | |a Epstein-Barr virus (EBV)+ nodal T- and NK-cell lymphoma (EBV+ nPTCL) is a peripheral T-cell lymphoma (PTCL) that presents as a primary nodal disease with T-cell phenotype and EBV harboring on tumor cells. To date, the genetic aspect of EBV+ nPTCL has not been fully investigated. 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 whose presence was associated with poor overall survival (p = 0.004). The RHOA p.Gly17Val mutation was identified in two patients who had TET2 and/or DNMT3A mutations. In four patients with TET2/DNMT3A alterations, blood cell-rich tissues (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 (SVs) were found frequent among the EBV genomes (63%). The most frequently identified type of SV was deletion. In one patient, four pieces of human chromosome 9, including PD-L1 were identified to be tandemly incorporated into the EBV genome. The 3'-untranslated region of PD-L1 was truncated, causing a high-level of PD-L1 protein expression. 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 | ||
| 650 | 4 | |a Journal Article | |
| 700 | 1 | |a Hamada, Motoharu |e verfasserin |4 aut | |
| 700 | 1 | |a Okamoto, Akinao |e verfasserin |4 aut | |
| 700 | 1 | |a Yamashita, Daisuke |e verfasserin |4 aut | |
| 700 | 1 | |a Miyoshi, Hiroaki |e verfasserin |4 aut | |
| 700 | 1 | |a Arai, Haruto |e verfasserin |4 aut | |
| 700 | 1 | |a Satou, Akira |e verfasserin |4 aut | |
| 700 | 1 | |a Gion, Yuka |e verfasserin |4 aut | |
| 700 | 1 | |a Sato, Yasuharu |e verfasserin |4 aut | |
| 700 | 1 | |a Tsuyuki, Yuta |e verfasserin |4 aut | |
| 700 | 1 | |a Miyata-Takata, Tomoko |e verfasserin |4 aut | |
| 700 | 1 | |a Takata, Katsuyoshi |e verfasserin |4 aut | |
| 700 | 1 | |a Asano, Naoko |e verfasserin |4 aut | |
| 700 | 1 | |a Takahashi, Emiko |e verfasserin |4 aut | |
| 700 | 1 | |a Ohshima, Koichi |e verfasserin |4 aut | |
| 700 | 1 | |a Tomita, Akihiro |e verfasserin |4 aut | |
| 700 | 1 | |a Hosoda, Waki |e verfasserin |4 aut | |
| 700 | 1 | |a Nakamura, Shigeo |e verfasserin |4 aut | |
| 700 | 1 | |a Okuno, Yusuke |e verfasserin |4 aut | |
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