Genomic landscape of T-cell lymphoblastic lymphoma

IF 7 2区 医学 Q1 ONCOLOGY Chinese Journal of Cancer Research Pub Date : 2022-04-30 DOI:10.21147/j.issn.1000-9604.2022.02.03
Zhaoming Li, Yue Song, Mingzhi Zhang, Yiming Wei, Hang Ruan
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引用次数: 3

Abstract

Objective T-cell lymphoblastic lymphoma (T-LBL) is an aggressive neoplasm of precursor T cells, however, detailed genome-wide sequencing of large T-LBL cohorts has not been performed due to its rarity. The purpose of this study was to identify putative driver genes in T-LBL. Methods To gain insight into the genetic mechanisms of T-LBL development, we performed whole-exome sequencing on 41 paired tumor-normal DNA samples from patients with T-LBL. Results We identified 32 putative driver genes using whole-exome sequencing in 41 T-LBL cases, many of which have not previously been described in T-LBL, such as Janus kinase 3 (JAK3), Janus kinase 1 (JAK1), Runt-related transcription factor 1 (RUNX1) and Wilms’ tumor suppressor gene 1 (WT1). When comparing the genetic alterations of T-LBL to T-cell acute lymphoblastic leukemia (T-ALL), we found that JAK-STAT and RAS pathway mutations were predominantly observed in T-LBL (58.5% and 34.1%, respectively), whereas Notch and cell cycle signaling pathways mutations were more prevalent in T-ALL. Notably, besides notch receptor 1 (NOTCH1), mutational status of plant homeodomain (PHD)-like finger protein 6 (PHF6) was identified as another independent factor for good prognosis. Of utmost interest is that co-existence of PHF6 and NOTCH1 mutation status might provide an alternative for early therapeutic stratification in T-LBL. Conclusions Together, our findings will not only provide new insights into the molecular and genetic mechanisms of T-LBL, but also have tangible implications for clinical practice.
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T细胞淋巴母细胞淋巴瘤的基因组景观
目的T细胞淋巴母细胞淋巴瘤(T-LBL)是前体T细胞的侵袭性肿瘤,然而 由于其罕见性,尚未进行大型T-LBL队列。本研究的目的是鉴定T-LBL中假定的驱动基因。方法为了深入了解T-LBL发生的遗传机制,我们对41份来自T-LBL患者的配对肿瘤正常DNA样本进行了全外显子组测序。结果我们在41例T-LBL病例中使用全外显子组测序鉴定了32个假定的驱动基因,其中许多先前未在T-LBL中描述,如Janus激酶3(JAK3)、Janus激酶1(JAK1)、Runt相关转录因子1(RUNX1)和Wilms抑癌基因1(WT1)。当比较T-LBL和T细胞急性淋巴细胞白血病(T-ALL)的基因改变时,我们发现JAK-STAT和RAS通路突变主要在T-LBL中观察到(分别为58.5%和34.1%),而Notch和细胞周期信号通路突变在T-ALL中更普遍。值得注意的是,除了notch受体1(NOTCH1)外,植物同源结构域(PHD)样指状蛋白6(PHF6)的突变状态被确定为预后良好的另一个独立因素。最令人感兴趣的是,PHF6和NOTCH1突变状态的共存可能为T-LBL的早期治疗分层提供一种替代方案。结论总之,我们的研究结果不仅将为T-LBL的分子和遗传机制提供新的见解,而且对临床实践具有实际意义。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
自引率
9.80%
发文量
1726
审稿时长
4.5 months
期刊介绍: Chinese Journal of Cancer Research (CJCR; Print ISSN: 1000-9604; Online ISSN:1993-0631) is published by AME Publishing Company in association with Chinese Anti-Cancer Association.It was launched in March 1995 as a quarterly publication and is now published bi-monthly since February 2013. CJCR is published bi-monthly in English, and is an international journal devoted to the life sciences and medical sciences. It publishes peer-reviewed original articles of basic investigations and clinical observations, reviews and brief communications providing a forum for the recent experimental and clinical advances in cancer research. This journal is indexed in Science Citation Index Expanded (SCIE), PubMed/PubMed Central (PMC), Scopus, SciSearch, Chemistry Abstracts (CA), the Excerpta Medica/EMBASE, Chinainfo, CNKI, CSCI, etc.
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