Bea Silvia, Zettl Andreas, Wright George, Salaverria Itziar, Jehn Philipp, Moreno Victor, Burek Christof, Ott German, Puig Xavier, Yang Liming, Lopez-Guillermo Armando, Chan Wing C, Greiner Timothy C, Weisenburger Dennis D, Armitage James O, Gascoyne Randy D, Connors Joseph M, Grogan Thomas M, Braziel Rita, Fisher Richard I, Smeland Erlend B, Kvaloy Stein, Holte Harald, Delabie Jan, Simon Richard, Powell John, Wilson Wyndham H, Jaffe Elaine S, Montserrat Emili, Muller-Hermelink Hans-Konrad, Staudt Louis M, Campo Elias, Rosenwald Andreas
Department of Pathology and Hematology Hospital Clinic, University of Barcelona, Spain.
Blood. 2005 Nov 1;106(9):3183-90. doi: 10.1182/blood-2005-04-1399. Epub 2005 Jul 26.
Gene-expression profiling has identified 3 major subgroups of diffuse large B-cell lymphoma (DLBCL): germinal center B-cell-like (GCB), activated B-cell-like (ABC), and primary mediastinal DLBCL (PMBCL). Using comparative genomic hybridization (CGH), we investigated the genetic alterations of 224 cases of untreated DLBCL (87 GCB-DLBCL, 77 ABC-DLBCL, 19 PMBCL, and 41 unclassified DLBCL) previously characterized by gene-expression profiling. The DLBCL subgroups differed significantly in the frequency of particular chromosomal aberrations. ABC-DLBCL had frequent trisomy 3, gains of 3q and 18q21-q22, and losses of 6q21-q22, whereas GCB-DLBCL had frequent gains of 12q12, and PMBCL had gains of 9p21-pter and 2p14-p16. Parallel analysis of CGH alterations, locus-specific gene-expression profiles, and global gene-expression signatures revealed that DNA amplifications and gains had a substantial impact on the expression of genes in the involved chromosomal regions, and some genes were overexpressed in a DLBCL subgroup-specific fashion. Unexpectedly, specific chromosomal alterations were associated with significant changes in gene-expression signatures that reflect various aspects of lymphoma cell biology as well as the host response to the lymphoma. In addition, gains involving the chromosomal region 3p11-p12 provided prognostic information that was statistically independent of the previously defined gene-expression-based survival model, thereby improving its predictive power.
基因表达谱分析已确定弥漫性大B细胞淋巴瘤（DLBCL）的3个主要亚组：生发中心B细胞样（GCB）、活化B细胞样（ABC）和原发性纵隔DLBCL（PMBCL）。我们使用比较基因组杂交（CGH）技术，研究了224例未经治疗的DLBCL（87例GCB-DLBCL、77例ABC-DLBCL、19例PMBCL和41例未分类DLBCL）的基因改变，这些病例先前已通过基因表达谱分析进行了特征描述。DLBCL亚组在特定染色体畸变的频率上有显著差异。ABC-DLBCL常见三体3、3q和18q21-q22增益以及6q21-q22缺失，而GCB-DLBCL常见12q12增益，PMBCL常见9p21-pter和2p14-p16增益。对CGH改变、基因座特异性基因表达谱和全基因组表达特征的平行分析表明，DNA扩增和增益对所涉及染色体区域的基因表达有重大影响，并且一些基因以DLBCL亚组特异性方式过表达。出乎意料的是，特定的染色体改变与基因表达特征的显著变化相关，这些变化反映了淋巴瘤细胞生物学的各个方面以及宿主对淋巴瘤的反应。此外，涉及染色体区域3p11-p12的增益提供了预后信息，该信息在统计学上独立于先前定义的基于基因表达的生存模型，从而提高了其预测能力。
