Genomic Mutation Profile of Primary Gastrointestinal Diffuse Large B-Cell Lymphoma.
Genomic Mutation Profile of Primary Gastrointestinal Diffuse Large B-Cell Lymphoma.
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原发性胃肠道弥漫性大 B 细胞淋巴瘤的基因组突变概况
DOI：
10.3389/fonc.2021.622648
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发表时间：
2021
影响因子：
4.7
通讯作者：
Wang Z
中科院分区：
文献类型：
--
作者：
Li P;Chai J;Chen Z;Liu Y;Wei J;Liu Y;Zhao D;Ma J;Wang K;Li X;Shao Y;Gong L;Zhang W;Guo S;Yan Q;Li M;Fan L;Wang Z
原发性胃肠道弥漫性大 B 细胞淋巴瘤 (GI-DLBCL) 是最常见的胃肠道淋巴瘤，但对其遗传特征知之甚少。我们对来自 GI-DLBCL 患者的 25 个原发肿瘤样本和 23 个匹配的正常组织样本进行了全外显子组测序。筛选致癌突变，分析基因突变与临床病理特征的相关性。 25 名 GI-DLBCL 患者被纳入基因突变分析，每名患者平均有 184 个（范围 79-382）个蛋白质改变变异。我们鉴定了 GI-DLBCL 中的复发性致癌突变，包括 TP53、MUC16、B2M、CCND3、HIST1H1C、NEB 和 ID3 中的突变。与结节性DLBCL相比，GI-DLBCL的TP53突变频率增加，PIM1、CREBBP、BCL2、KMT2D和EZH2突变频率降低。此外，GI-DLBCL 在睾丸和中枢神经系统中表现出比 DLBCL 更少的 MYD88 和 CD79B 突变。具有 HLA-B、MEF2A、RHOA 和 NAV3 突变的 GI-DLBCL 表现出高增殖指数的趋势。 MUC16和ETV6突变常发生在临床分期早期的肿瘤中。我们的数据提供了对一小部分 GI-DLBCL 突变情况的全面了解。 GI-DLBCL 的基因突变谱与淋巴结 DLBCL 和免疫豁免部位的 DLBCL 不同。不同的突变基因与NF-κB和JAK-STAT通路相关，导致DLBCL发生的不同发病机制可能受到组织微环境的影响。基因改变的差异可能影响 GI-DLBCL 的临床病理特征。
Primary gastrointestinal diffuse large B-cell lymphoma (GI-DLBCL) is the most common gastrointestinal lymphoma, but its genetic features are poorly understood. We performed whole-exome sequencing of 25 primary tumor samples from patients with GI-DLBCL and 23 matched normal tissue samples. Oncogenic mutations were screened, and the correlations between genetic mutations and clinicopathological characteristics were analyzed. Twenty-five patients with GI-DLBCL were enrolled in the genetic mutation analysis with a median of 184 (range 79–382) protein-altering variants per patient. We identified recurrent oncogenic mutations in GI-DLBCL, including those in TP53, MUC16, B2M, CCND3, HIST1H1C, NEB, and ID3. Compared with nodal DLBCL, GI-DLBCL exhibited an increased mutation frequency of TP53 and reduced mutation frequencies of PIM1, CREBBP, BCL2, KMT2D, and EZH2. Moreover, GI-DLBCL exhibited fewer MYD88 and CD79B mutations than DLBCL in the testis and central nervous system. GI-DLBCLs with HLA-B, MEF2A, RHOA, and NAV3 mutations exhibited a tendency toward a high proliferation index. MUC16 and ETV6 mutations often occurred in tumors with early clinical staging. Our data provide a comprehensive understanding of the landscape of mutations in a small subset of GI-DLBCLs. The genetic mutation profiles of GI-DLBCL differ from those of nodal DLBCL and DLBCL in immune-privileged sites. The different mutated genes are related to the NF-κB and JAK-STAT pathways, and the different pathogenetic mechanisms leading to the development of DLBCL may be influenced by the tissue microenvironment. Differences in genetic alterations might influence the clinicopathological characteristics of GI-DLBCL.
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影响因子：
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作者：
Cai YB;Chen HY;He JJ;Hu YT;Yang Q;Chen LB;Xiao Q;Ding KF
通讯作者：
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Lenz, Georg;Davis, R. Eric;Staudt, Louis M.
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Staudt, Louis M.
影响因子：
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Ortega-Molina A;Boss IW;Canela A;Pan H;Jiang Y;Zhao C;Jiang M;Hu D;Agirre X;Niesvizky I;Lee JE;Chen HT;Ennishi D;Scott DW;Mottok A;Hother C;Liu S;Cao XJ;Tam W;Shaknovich R;Garcia BA;Gascoyne RD;Ge K;Shilatifard A;Elemento O;Nussenzweig A;Melnick AM;Wendel HG
通讯作者：
Wendel HG
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