Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes.
Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes.
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DOI：
10.1038/s41591-018-0016-8
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发表时间：
2018-05
期刊：
影响因子：
82.9
通讯作者：
Shipp MA
中科院分区：
文献类型：
--
作者：
Chapuy B;Stewart C;Dunford AJ;Kim J;Kamburov A;Redd RA;Lawrence MS;Roemer MGM;Li AJ;Ziepert M;Staiger AM;Wala JA;Ducar MD;Leshchiner I;Rheinbay E;Taylor-Weiner A;Coughlin CA;Hess JM;Pedamallu CS;Livitz D;Rosebrock D;Rosenberg M;Tracy AA;Horn H;van Hummelen P;Feldman AL;Link BK;Novak AJ;Cerhan JR;Habermann TM;Siebert R;Rosenwald A;Thorner AR;Meyerson ML;Golub TR;Beroukhim R;Wulf GG;Ott G;Rodig SJ;Monti S;Neuberg DS;Loeffler M;Pfreundschuh M;Trümper L;Getz G;Shipp MA
弥漫性大B细胞淋巴瘤（DLBCL）是成人中最常见的淋巴恶性肿瘤，是一种临床和遗传异质性疾病，其进一步分为转录定义的活化B细胞（ABC）和生发中心B细胞（GCB）亚型。我们对304例原发性DLBCL进行了全面的遗传分析，确定了低频改变，捕获了复发突变，体细胞拷贝数改变（SCNA）和结构变异（SV），并在具有可用结果数据的患者中定义了坐标签名。我们使用共识聚类整合了这些遗传驱动因素，并确定了五个强大的DLBCL子集，包括一组先前未被识别的滤泡外/边缘区起源的低风险ABC-DLBCL;两个不同的GCB-DLBCL子集，具有不同的结局和靶向改变;以及一个ABC/GCB独立组，具有TP 53的双等位基因失活，CDKN 2A丢失和相关的基因组不稳定性。新表征的子集的遗传特征、它们的突变特征和鉴定的改变的时间顺序为DLBCL发病机制提供了新的见解。协调遗传标记还预测独立于临床国际预后指数的结果，并提出新的联合治疗策略。更广泛地说，我们的结果为可操作的DLBCL分类提供了路线图。
Diffuse large B-cell lymphoma (DLBCL), the most common lymphoid malignancy in adults, is a clinically and genetically heterogeneous disease that is further classified into transcriptionally defined activated B-cell (ABC) and germinal center B-cell (GCB) subtypes. We carried out a a comprehensive genetic analysis of 304 primary DLBCLs that identifies low-frequency alterations, captured recurrent mutations, somatic copy number alterations (SCNAs) and structural variants (SVs), and defined coordinate signatures in patients with available outcome data. We integrated these genetic drivers using consensus clustering and identified five robust DLBCL subsets, including a previously unrecognized group of low-risk ABC-DLBCLs of extrafollicular/marginal zone origin; two distinct subsets of GCB-DLBCLs with different outcomes and targetable alterations; and an ABC/GCB-independent group with biallelic inactivation of TP53, CDKN2A loss and associated genomic instability. The genetic features of the newly characterized subsets, their mutational signatures and the temporal ordering of identified alterations provide new insights into DLBCL pathogenesis. The coordinate genetic signatures also predict outcome independent of the clinical International Prognostic Index and suggest new combination treatment strategies. More broadly, our results provide a roadmap for an actionable DLBCL classification.
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影响因子：
64.5
作者：
Cancer Genome Atlas Research Network
通讯作者：
Cancer Genome Atlas Research Network
影响因子：
10.1
作者：
Dierlamm, Judith;Penas, Eva M. Murga;Siebert, Reiner
通讯作者：
Siebert, Reiner
影响因子：
50.3
作者：
Chen L;Monti S;Juszczynski P;Ouyang J;Chapuy B;Neuberg D;Doench JG;Bogusz AM;Habermann TM;Dogan A;Witzig TE;Kutok JL;Rodig SJ;Golub T;Shipp MA
通讯作者：
Shipp MA
影响因子：
20.3
作者：
Green, Michael R.;Monti, Stefano;Shipp, Margaret A.
通讯作者：
Shipp, Margaret A.
淋巴瘤中HVEM肿瘤抑制剂的丧失和修饰的CAR-T细胞恢复。
影响因子：
64.5
作者：
Boice M;Salloum D;Mourcin F;Sanghvi V;Amin R;Oricchio E;Jiang M;Mottok A;Denis-Lagache N;Ciriello G;Tam W;Teruya-Feldstein J;de Stanchina E;Chan WC;Malek SN;Ennishi D;Brentjens RJ;Gascoyne RD;Cogné M;Tarte K;Wendel HG
通讯作者：
Wendel HG