生物
爱泼斯坦-巴尔病毒
淋巴瘤
基因组
T细胞淋巴瘤
病毒
癌症研究
病毒学
基因
遗传学
免疫学
作者
Seiichi Kato,Motoharu Hamada,Akinao Okamoto,Daisuke Yamashita,Hiroaki Miyoshi,Hidee Arai,Akira Satou,Yuka Gion,Yasuharu Sato,Yuta Tsuyuki,Tomoko Miyata‐Takata,Katsuyoshi Takata,Naoki Asano,Emiko Takahashi,Koichi Ohshima,Akihiro Tomita,Waki Hosoda,Shigeo Nakamura,Yusuke Okuno
出处
期刊:Blood Advances
[American Society of Hematology]
日期:2024-03-01
被引量:1
标识
DOI:10.1182/bloodadvances.2023012019
摘要
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.
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