文章：

9p24.1扩增在弥漫大B细胞淋巴瘤中识别出一组类似于原发性纵隔大B细胞淋巴瘤的独特病例

Amplification of 9p24.1 in diffuse large B-cell lymphoma identifies a unique subset of cases that resemble primary mediastinal large B-cell lymphoma

原文发布日期：2019-08-30

DOI: 10.1038/s41408-019-0233-5

类型: Article

开放获取: 是

英文摘要：

Copy number alterations (CNAs) of 9p24.1 occur frequently in Hodgkin lymphoma, primary mediastinal large B-cell lymphoma (PMBCL), primary central nervous system lymphoma, and primary testicular lymphoma, resulting in overexpression of PD-L1 and sensitivity to PD-1 blockade-based immunotherapy. While 9p24.1 CNA was also reported in diffuse large B-cell lymphoma (DLBCL), little is known about its molecular or clinical significance. In this study, we analyzed the prevalence of 9p24.1 CNA in newly diagnosed DLBCL and examined its association with PD-L1, PD-L2, and JAK2 expression, clinical characteristics, and outcome. We found that 10% of DLBCL cases had CNA of 9p24.1, with 6.5% gains, and 3.5% amplifications. Only the cases with a 9p24.1 amplification had high levels of PD-L1, PD-L2, and JAK2 expression. Gains or amplifications of 9p24.1 were associated with a younger age and the ABC/non-GCB subtype. Compared with DLBCL cases without 9p24.1 CNA, the cases with a 9p24.1 amplification had a trend of better event-free survival. Furthermore, the amplification cases had a gene expression and mutation profile similar to those of PMBCL. Our data suggest that amplification of 9p24.1 identifies a unique subset of DLBCL with clinical and molecular features resembling PMBCL that may be amenable to PD-1 blockade-based immunotherapy.
 

摘要翻译： 

9p24.1的拷贝数改变在霍奇金淋巴瘤、原发性纵隔大B细胞淋巴瘤、原发性中枢神经系统淋巴瘤和原发性睾丸淋巴瘤中频繁发生，导致PD-L1过度表达并对基于PD-1阻断的免疫疗法产生敏感性。虽然9p24.1的拷贝数改变在弥漫性大B细胞淋巴瘤中也有报道，但其分子或临床意义尚不明确。本研究分析了新诊断的弥漫性大B细胞淋巴瘤中9p24.1拷贝数改变的普遍性，并探讨了其与PD-L1、PD-L2和JAK2表达、临床特征及预后的关系。我们发现10%的弥漫性大B细胞淋巴瘤病例存在9p24.1拷贝数改变，其中6.5%为获得性改变，3.5%为扩增性改变。只有9p24.1扩增的病例表现出高水平的PD-L1、PD-L2和JAK2表达。9p24.1的获得或扩增与较年轻的年龄和ABC/非GCB亚型相关。与无9p24.1拷贝数改变的弥漫性大B细胞淋巴瘤病例相比，具有9p24.1扩增的病例显示出更好的无事件生存趋势。此外，扩增病例的基因表达和突变特征与原发性纵隔大B细胞淋巴瘤相似。我们的数据表明，9p24.1扩增识别出一种具有类似于原发性纵隔大B细胞淋巴瘤临床和分子特征的独特弥漫性大B细胞淋巴瘤亚群，可能适用于基于PD-1阻断的免疫疗法。

原文链接：

Amplification of 9p24.1 in diffuse large B-cell lymphoma identifies a unique subset of cases that resemble primary mediastinal large B-cell lymphoma