Zhaoming Li, Yue Song, Mingzhi Zhang, Yiming Wei, Hang Ruan
{"title":"Genomic landscape of T-cell lymphoblastic lymphoma","authors":"Zhaoming Li, Yue Song, Mingzhi Zhang, Yiming Wei, Hang Ruan","doi":"10.21147/j.issn.1000-9604.2022.02.03","DOIUrl":null,"url":null,"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.","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":"34 1","pages":"83 - 94"},"PeriodicalIF":7.0000,"publicationDate":"2022-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"3","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Chinese Journal of Cancer Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.21147/j.issn.1000-9604.2022.02.03","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
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.
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.