Paper_7: Natural killer/T cell淋巴瘤的基因组、转录组特征

Highlights

1. Integrated analysis provides insight into the molecular classification in NKTCL
2. EBV lytic genes play an important role on NKTCL pathogenesis
3. Genomic alteration-based molecular subtypes associate with clinical outcomes
4. MYC, histone acetylation, and PD-L1/2 are potential therapeutic targets of NKTCL

Summary

Natural killer/T cell lymphoma (NKTCL) is an aggressive and heterogeneous entity of non-Hodgkin lymphoma, strongly associated with Epstein-Barr virus (EBV) infection. To identify molecular subtypes of NKTCL based on genomic structural alterations and EBV sequences, we performed multi-omics study on 128 biopsy samples of newly diagnosed NKTCL and defined three prominent subtypes, which differ significantly in cell of origin, EBV gene expression, transcriptional signatures, and responses to asparaginase-based regimens and targeted therapy. Our findings thus identify molecular networks of EBV-associated pathogenesis and suggest potential clinical strategies on NKTCL.

Highlights

1.整合分析有助于深入了解NKTCL中的分子分型
2.EBV lytic genes在NKTCL发病机理中起重要作用
3.基于基因组差异的分子亚型与临床结果相关
4.MYC，组蛋白乙酰化和PD-L1 / 2是NKTCL的潜在治疗靶标

Summary

天然杀伤/ T细胞淋巴瘤（NKTCL）是非霍奇金淋巴瘤的侵袭性和异质性实体，与Epstein-Barr病毒（EBV）感染密切相关。 为了根据基因组结构改变和EBV序列鉴定NKTCL的分子亚型，我们对128例新诊断的NKTCL活检样本进行了多组学研究，并定义了三种突出的亚型，它们在起源细胞，EBV基因表达，转录特征， 以及对基于天冬酰胺酶的治疗方案和靶向治疗的反应等方面存在差异。 因此，我们的发现确定了EBV相关发病机理的分子网络，并提出了NKTCL的潜在临床策略。