A Probabilistic Classification Tool for Genetic Subtypes of Diffuse Large B Cell Lymphoma with Therapeutic Implications.
A Probabilistic Classification Tool for Genetic Subtypes of Diffuse Large B Cell Lymphoma with Therapeutic Implications.
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DOI：
10.1016/j.ccell.2020.03.015
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发表时间：
2020-04-13
期刊：
影响因子：
50.3
通讯作者：
Staudt LM
中科院分区：
文献类型：
--
作者：
Wright GW;Huang DW;Phelan JD;Coulibaly ZA;Roulland S;Young RM;Wang JQ;Schmitz R;Morin RD;Tang J;Jiang A;Bagaev A;Plotnikova O;Kotlov N;Johnson CA;Wilson WH;Scott DW;Staudt LM
弥漫性大B细胞淋巴瘤（DLBCL）的精确医学方法的发展受到其明显的遗传、表型和临床异质性的混淆。最近的多平台基因组研究揭示了DLBCL的遗传亚型的存在，使用聚类方法。在这里，我们描述了一种算法，该算法根据患者的遗传特征确定患者的淋巴瘤属于七种遗传亚型之一的概率。这种分类揭示了这些DLBCL亚型和各种惰性和淋巴结淋巴瘤类型之间的遗传相似性，表明共同的发病机制。这些基因亚型也有不同的基因表达谱，免疫微环境和免疫化疗后的结果。基因亚型模型的功能分析突出了靶向治疗的明显弱点，支持在精准医学试验中使用这种分类。
The development of precision medicine approaches for diffuse large B cell lymphoma (DLBCL) is confounded by its pronounced genetic, phenotypic, and clinical heterogeneity. Recent multiplatform genomic studies revealed the existence of genetic subtypes of DLBCL using clustering methodologies. Here, we describe an algorithm that determines the probability that a patient’s lymphoma belongs to one of seven genetic subtypes based on its genetic features. This classification reveals genetic similarities between these DLBCL subtypes and various indolent and extranodal lymphoma types, suggesting a shared pathogenesis. These genetic subtypes also have distinct gene expression profiles, immune microenvironments, and outcomes following immunochemotherapy. Functional analysis of genetic subtype models highlights distinct vulnerabilities to targeted therapy, supporting the use of this classification in precision medicine trials.
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影响因子：
46.9
作者：
Bolotin DA;Poslavsky S;Davydov AN;Frenkel FE;Fanchi L;Zolotareva OI;Hemmers S;Putintseva EV;Obraztsova AS;Shugay M;Ataullakhanov RI;Rudensky AY;Schumacher TN;Chudakov DM
通讯作者：
Chudakov DM
影响因子：
56.9
作者：
Celeste, A;Petersen, S;Nussenzweig, A
通讯作者：
Nussenzweig, A
影响因子：
45.3
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Beà, S;Colomo, L;Campo, E
通讯作者：
Campo, E
影响因子：
30.5
作者：
Dogan, Ismail;Bertocci, Barbara;Weill, Jean-Claude
通讯作者：
Weill, Jean-Claude
影响因子：
82.9
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
通讯作者：
Shipp MA