Mutations Affecting Genes in the Proximal T-Cell Receptor Signaling Pathway in Peripheral T-Cell Lymphoma.
Mutations Affecting Genes in the Proximal T-Cell Receptor Signaling Pathway in Peripheral T-Cell Lymphoma.
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外周T细胞淋巴瘤近端T细胞受体信号通路中影响基因的突变
DOI：
10.3390/cancers14153716
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发表时间：
2022-07-29
期刊：
影响因子：
5.2
通讯作者：
Chan, Wing C. (John)
中科院分区：
文献类型：
--
作者：
Liu, Xiaoqian;Ning, Jinyao;Liu, Xuxiang;Chan, Wing C. (John)
下一代测序技术的出现使外周T细胞淋巴瘤（PTCL）的发病机制和生物学的基因组研究取得了快速进展。与近端TCR信号通路相关的基因中的复发性突变和融合已被鉴定，并在PTCL中显示出重要的致病作用。在这篇综述中，我们总结了在PTCL患者的不同亚组中发现的TCR信号的基因组改变以及这些改变对TCR信号和下游通路的功能影响。我们还讨论了新的药物，可以靶向TCR相关的突变，并可能持有改善PTCL治疗的承诺。外周T细胞淋巴瘤（PTCL）包括一组异质性成熟T细胞恶性肿瘤。在临床前和临床研究中已经鉴定了与近端TCR信号传导途径相关的基因中的复发性激活突变和融合。本文综述了影响近端TCR信号转导的基因改变，从不同的PTCL亚群和TCR信号转导和下游通路的功能影响。这些遗传异常主要包括错义突变、偶尔的插入缺失和涉及CD 28、CARD 11、GTdR RHOA、鸟嘌呤核苷酸交换因子VAV 1和激酶（包括FYN、ITK、PLCG 1、PKCB和PI 3 K亚基）的基因融合。大多数这些畸变是激活突变，可以潜在地被抑制剂靶向，其中一些正在测试中的临床试验，简要概述了这一审查。最后，我们专注于最近确定的PTCL-NOS亚组的分子病理学，并强调与PTCL-GATA 3相关的独特遗传特征。
The advent of next-generation sequencing (NGS) has allowed rapid advances in genomic studies on the pathogenesis and biology of peripheral T-cell lymphoma (PTCL). Recurrent mutations and fusions in genes related to the proximal TCR signaling pathway have been identified and show an important pathogenic role in PTCL. In this review, we summarize the genomic alterations in TCR signaling identified in different subgroups of PTCL patients and the functional impact of these alterations on TCR signaling and downstream pathways. We also discuss novel agents that could target TCR-related mutations and may hold promise for improving the treatment of PTCL. Peripheral T-cell lymphoma (PTCL) comprises a heterogeneous group of mature T-cell malignancies. Recurrent activating mutations and fusions in genes related to the proximal TCR signaling pathway have been identified in preclinical and clinical studies. This review summarizes the genetic alterations affecting proximal TCR signaling identified from different subgroups of PTCL and the functional impact on TCR signaling and downstream pathways. These genetic abnormalities include mostly missense mutations, occasional indels, and gene fusions involving CD28, CARD11, the GTPase RHOA, the guanine nucleotide exchange factor VAV1, and kinases including FYN, ITK, PLCG1, PKCB, and PI3K subunits. Most of these aberrations are activating mutations that can potentially be targeted by inhibitors, some of which are being tested in clinical trials that are briefly outlined in this review. Finally, we focus on the molecular pathology of recently identified subgroups of PTCL-NOS and highlight the unique genetic profiles associated with PTCL-GATA3.
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影响因子：
11.4
作者：
Fujisawa M;Sakata-Yanagimoto M;Nishizawa S;Komori D;Gershon P;Kiryu M;Tanzima S;Fukumoto K;Enami T;Muratani M;Yoshida K;Ogawa S;Matsue K;Nakamura N;Takeuchi K;Izutsu K;Fujimoto K;Teshima T;Miyoshi H;Gaulard P;Ohshima K;Chiba S
通讯作者：
Chiba S
影响因子：
50.3
作者：
Cortes JR;Ambesi-Impiombato A;Couronné L;Quinn SA;Kim CS;da Silva Almeida AC;West Z;Belver L;Martin MS;Scourzic L;Bhagat G;Bernard OA;Ferrando AA;Palomero T
通讯作者：
Palomero T
影响因子：
20.3
作者：
Horwitz, Steven M.;Koch, Raphael;Weinstock, David M.
通讯作者：
Weinstock, David M.
影响因子：
32.4
作者：
Esensten JH;Helou YA;Chopra G;Weiss A;Bluestone JA
通讯作者：
Bluestone JA
影响因子：
5.4
作者：
Butzmann, Alexandra;Sridhar, Kaushik;Ohgami, Robert Shigeo
通讯作者：
Ohgami, Robert Shigeo