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.

Zhaoming Li;Yue Song;Mingzhi Zhang;Yiming Wei;Hang Ruan

Department of Oncology,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China;State Key Laboratory of Esophageal Cancer Prevention&Treatment and Henan Key Laboratory for Esophageal Cancer Research,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China

中国癌症研究（英文版）

[1]Zhaoming Li;Yue Song;Mingzhi Zhang;Yiming Wei;Hang Ruan-.Genomic landscape of T-cell lymphoblastic lymphoma)[J].中国癌症研究（英文版）,2022(02):83-94

Genomic,landscape,lymphoblastic,lymphoma,Objective,LBL,aggressive,neoplasm,precursor,cells,however,detailed,genome,wide,sequencing,large,cohorts,has,been,performed,due,its,rarity,purpose,this,study,was,identify,putative,driver,genes,Methods,gain,into,genetic,mechanisms,development,whole,exome,paired,tumor,normal,samples,from,patients,Results,We,identified,using,cases,many,which,have,previously,described,such,Janus,kinase,JAK3,JAK1,Runt,related,transcription,RUNX1,Wilms,suppressor,WT1,When,comparing,alterations,acute,leukemia,ALL,found,that,STAT,RAS,mutations,were,predominantly,observed,respectively,whereas,Notch,cycle,signaling,pathways,more,prevalent,Notably,besides,notch,receptor,NOTCH1,mutational,status,plant,homeodomain,PHD,like,finger,protein,PHF6,another,independent,good,prognosis,Of,utmost,interest,existence,might,provide,alternative,early,therapeutic,stratification,Conclusions,Together,our,findings,will,only,new,insights,molecular,but,also,tangible,implications,clinical,practice

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