摘要

Peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS) is a diagnosis of exclusion, being the most common entity in mature T-cell neoplasms, and its molecular pathogenesis remains significantly understudied. Here, combining whole-exome and targeted-capture sequencing, gene-expression profiling, and immunohistochemical analysis of tumor samples from 133 cases, we have delineated the entire landscape of somatic alterations, and discovered frequently affected driver pathways in PTCL, NOS, with and without a T-follicular helper (TFH) cell phenotype. In addition to previously reported mutational targets, we identified a number of novel recurrently altered genes, such as KMT2C, SETD1B, YTHDF2, and PDCD1. We integrated these genetic drivers using hierarchical clustering and identified a previously undescribed molecular subtype characterized by TP53 and/or CDKN2A mutations and deletions in non-TFH PTCL, NOS. This subtype exhibited different prognosis and unique genetic features associated with extensive chromosomal instability, which preferentially affected molecules involved in immune escape and transcriptional regulation, such as HLA-A/B and IKZF2. Taken together, our findings provide novel insights into the molecular pathogenesis of PTCL, NOS by highlighting their genetic heterogeneity. These results should help to devise a novel molecular classification of PTCLs and to exploit a new therapeutic strategy for this group of aggressive malignancies.

译文

外周 T 细胞淋巴瘤,未另行指定 (PTCL,NOS) 是一种排除的诊断,是成熟 T 细胞肿瘤中最常见的实体,其分子发病机制仍有待进一步研究。在这里,结合来自 133 个病例的肿瘤样本的全 exome 和靶向捕获测序、基因表达谱和免疫组织化学分析,我们描绘了体细胞改变的整个景观, 并在 PTCL 、 NOS 中发现了经常受影响的驱动通路,包括和不包括 T-滤泡辅助细胞 (TFH) 表型。除了之前报道的突变靶点,我们还鉴定了一些新的反复改变的基因,如 KMT2C 、 SETD1B 、 YTHDF2 和 pdcd1。我们使用分层聚类整合了这些遗传驱动因素,并鉴定了一种先前未描述的分子亚型,其特征是非 TFH PTCL,NOS 中的 TP53 和/或 CDKN2A 突变和缺失。这种亚型表现出不同的预后和与广泛染色体不稳定相关的独特遗传特征,染色体不稳定优先影响参与免疫逃逸和转录调控的分子,如 HLA-A/B 和 ikzf2。综上所述,我们的发现通过突出 PTCL 、 NOS 的遗传异质性,为 PTCL 、 NOS 的分子发病机制提供了新的见解。这些结果将有助于设计一种新的 PTCLs 分子分类,并为这组侵袭性恶性肿瘤开发一种新的治疗策略。

peripheral T-cell lymphoma

肿瘤 淋巴瘤 疾病
概述  :  

外周T细胞淋巴瘤,简称PTCL,是一组高度异质性的淋巴细胞异常恶性增殖性疾病。在我国,PTCL的病例占非霍奇金淋巴瘤25%~30%,显著高于欧美国家的10%-15%。据2008年WHO造血与淋巴组织肿瘤的分类标准,PTCL共包含22个亚型。我国最常见的亚型为结外NK/T 细胞淋巴瘤(鼻型);PTCL-非特指型;T 淋巴母细胞性淋巴瘤/白血病等。这些都属于外周T细胞淋巴瘤的范畴,无论是查询治疗方法还是最新动态都归类在PTCL中。 临床特征PTCL常见的临床表现为全身淋巴结肿大和/或结

Peripheral   英 /pə'rɪf(ə)r(ə)l/   美 /pə'rɪfərəl/

释    义   adj. 外围的;次要的;(神经)末梢区域的;n. 外部设备

同根词   peripherally adv. 周边地;外围地;次要地;periphery n. 外围,边缘;圆周;圆柱体表面

例    句   Objective:To study the application and significance of making chromosome specim peripheral blood lymphocyte(PBL) by large volume culture for students experiment. 目的: 探讨大体积培养人外周血淋巴细胞(PBL)染色体标本技术在学生实验中的应用及意义。

 

Lymphoma   英 /lɪm'fəʊmə/   美 /lɪm'fomə/

释    义   n. [肿瘤] 淋巴瘤;复数 lymphomas或lymphomata

同根词   lymphatic adj. 淋巴的;含淋巴的;lymphocytic adj. 淋巴细胞的;淋巴球的;lymphatic n. 淋巴管;淋巴腺;lymphocytosis n. 淋巴球增多;淋巴球过多症;lymphopoiesis n. 淋巴组织生成;淋巴细胞增殖

例    句   No two people with leukemia, lymphoma or myeloma are alike, nor are any two relatives or friends of someone with one of these illnesses the same. 没有任何两个白血病、淋巴瘤或者骨髓瘤的患者是完全相同的,同样,他们的亲戚朋友也不会。

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