Genomic landscape of T-cell lymphoblastic lymphoma

作     者：Zhaoming Li Yue Song Mingzhi Zhang Yiming Wei Hang Ruan Zhaoming Li;Yue Song;Mingzhi Zhang;Yiming Wei;Hang Ruan

作者机构：Department of Oncologythe First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China State Key Laboratory of Esophageal Cancer Prevention&Treatment and Henan Key Laboratory for Esophageal Cancer Researchthe First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China 

出 版 物：《Chinese Journal of Cancer Research》 (中国癌症研究（英文版）)

年 卷 期：2022年第34卷第2期

页      面：83-94页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China (No. U1904139 and 82070209)。 

主　　题：T-cell lymphoblastic lymphoma PHF6 NOTCH1 mutation 

摘      要：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), Runtrelated 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.