Comprehensive Genetic Profiling Reveals Frequent Alterations of Driver Genes on the X Chromosome in Extranodal NK/T-cell Lymphoma

生物 癌症研究 基因 淋巴瘤 遗传学 免疫学
作者
Yuta Ito,Amira Marouf,Yasunori Kogure,Junji Koya,Raphaël Liévin,Julie Bruneau,Mariko Tabata,Yuki Saito,Sumito Shingaki,Mitsuhiro Yuasa,K. Yamaguchi,Koichi Murakami,Robert Weil,Manon Vavasseur,Guillaume P. Andrieu,Mehdi Latiri,Layla Veleanu,Michaël Dussiot,Isabelle André‐Schmutz,Akshay Joshi,Chantal Lagresle‐Peyrou,Aude Magérus‐Chatinet,Sammara Chaubard,David Lavergne,Emmanuel Bachy,Erika Brunet,Virginie Fataccioli,Chantal Brouzes,Camille Laurent,Laurence de Leval,Alexandra Traverse-Gléhen,Céline Bossard,Marie Parrens,Véronique Meignin,Laure Philippe,Julien Rossignol,Felipe Suárez,Jean‐Marie Michot,Olivier Tournilhac,Gandhi Damaj,François Lemonnier,Christine Bôle‐Feysot,Patrick Nitschké,Bruno Tesson,Cécile Laurent,Thierry Jo Molina,Vahid Asnafi,Yosaku Watatani,Kenichi Chiba,Ai Okada,Yuichi Shiraishi,Sachiko Tsukita,Koji Izutsu,Hiroaki Miyoshi,Koichi Ohshima,Seiji Sakata,Akito Dobashi,Kengo Takeuchi,Masashi Sanada,Philippe Gaulard,Arnaud Jaccard,Seishi Ogawa,Olivier Hermine,Keisuke Kataoka,Lucile Couronné
出处
期刊:Cancer Research [American Association for Cancer Research]
卷期号:84 (13): 2181-2201 被引量:1
标识
DOI:10.1158/0008-5472.can-24-0132
摘要

Extranodal NK/T-cell lymphoma (ENKTCL) is an Epstein-Barr virus (EBV)-related neoplasm with male dominance and a poor prognosis. A better understanding of the genetic alterations and their functional roles in ENKTCL could help improve patient stratification and treatments. In this study, we performed a comprehensive genetic analysis of 178 ENKTCL cases to delineate the landscape of mutations, copy number alterations (CNA), and structural variations, identifying 34 driver genes including six previously unappreciated ones, namely, HLA-B, HLA-C, ROBO1, CD58, POT1, and MAP2K1. Among them, CD274 (24%) was the most frequently altered, followed by TP53 (20%), CDKN2A (19%), ARID1A (15%), HLA-A (15%), BCOR (14%), and MSN (14%). Chromosome X losses were the most common arm-level CNAs in females (∼40%), and alterations of four X-linked driver genes (MSN, BCOR, DDX3X, and KDM6A) were more frequent in males and females harboring chromosome X losses. Among X-linked drivers, MSN was the most recurrently altered, and its expression was lost in approximately one-third of cases using immunohistochemical analysis. Functional studies of human cell lines showed that MSN disruption promoted cell proliferation and NF-κB activation. Moreover, MSN inactivation increased sensitivity to NF-κB inhibition in vitro and in vivo. In addition, recurrent deletions were observed at the origin of replication in the EBV genome (6%). Finally, by integrating the 34 drivers and 19 significant arm-level CNAs, nonnegative matrix factorization and consensus clustering identified two molecular groups with different genetic features and prognoses irrespective of clinical prognostic factors. Together, these findings could help improve diagnostic and therapeutic strategies in ENKTCL. Significance: Integrative genetic analyses and functional studies in extranodal NK/T-cell lymphoma identify frequent disruptions of X-linked drivers, reveal prognostic molecular subgroups, and uncover recurrent MSN alterations that confer sensitivity to NF-κB inhibition.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
1秒前
1秒前
汉德萌多林完成签到,获得积分10
1秒前
安静达完成签到,获得积分10
1秒前
more完成签到,获得积分20
2秒前
2秒前
迷路芝麻完成签到,获得积分10
3秒前
zzz发布了新的文献求助10
4秒前
renhu发布了新的文献求助30
5秒前
冷静灵竹完成签到,获得积分10
8秒前
英勇的水壶完成签到,获得积分20
10秒前
wulixin完成签到,获得积分10
10秒前
Gardener关注了科研通微信公众号
11秒前
11秒前
鲤鱼香之完成签到,获得积分20
12秒前
renhu完成签到,获得积分10
13秒前
正霖完成签到,获得积分10
14秒前
16秒前
17秒前
平淡妙梦完成签到 ,获得积分10
20秒前
空空完成签到,获得积分10
20秒前
桐桐应助麻薯头头采纳,获得10
24秒前
25秒前
步步完成签到 ,获得积分10
27秒前
30秒前
saveMA发布了新的文献求助10
31秒前
健身boy完成签到,获得积分10
32秒前
酷波er应助科研通管家采纳,获得10
32秒前
搜集达人应助科研通管家采纳,获得10
32秒前
小马甲应助科研通管家采纳,获得10
32秒前
传奇3应助科研通管家采纳,获得10
32秒前
Owen应助科研通管家采纳,获得10
32秒前
上官若男应助科研通管家采纳,获得10
32秒前
33秒前
循环bug完成签到,获得积分10
34秒前
35秒前
SonRisa完成签到,获得积分10
36秒前
寒冷海云发布了新的文献求助10
37秒前
Sea完成签到,获得积分10
38秒前
jihaowen完成签到,获得积分20
40秒前
高分求助中
Kinetics of the Esterification Between 2-[(4-hydroxybutoxy)carbonyl] Benzoic Acid with 1,4-Butanediol: Tetrabutyl Orthotitanate as Catalyst 1000
The Young builders of New china : the visit of the delegation of the WFDY to the Chinese People's Republic 1000
Rechtsphilosophie 1000
Bayesian Models of Cognition:Reverse Engineering the Mind 888
Handbook of Qualitative Cross-Cultural Research Methods 600
Very-high-order BVD Schemes Using β-variable THINC Method 568
Chen Hansheng: China’s Last Romantic Revolutionary 500
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3137721
求助须知:如何正确求助?哪些是违规求助? 2788646
关于积分的说明 7787887
捐赠科研通 2445011
什么是DOI,文献DOI怎么找? 1300139
科研通“疑难数据库(出版商)”最低求助积分说明 625814
版权声明 601043