文章：

从华氏巨球蛋白血症到侵袭性弥漫大B细胞淋巴瘤：导致转化的异常的全外显子组分析

From Waldenström’s macroglobulinemia to aggressive diffuse large B-cell lymphoma: a whole-exome analysis of abnormalities leading to transformation

原文发布日期：2017-08-25

DOI: 10.1038/bcj.2017.72

类型: Original Article

开放获取: 是

英文摘要：

Transformation of Waldenström’s macroglobulinemia (WM) to diffuse large B-cell lymphoma (DLBCL) occurs in up to 10% of patients and is associated with an adverse outcome. Here we performed the first whole-exome sequencing study of WM patients who evolved to DLBCL and report the genetic alterations that may drive this process. Our results demonstrate that transformation depends on the frequency and specificity of acquired variants, rather than on the duration of its evolution. We did not find a common pattern of mutations at diagnosis or transformation; however, there were certain abnormalities that were present in a high proportion of clonal tumor cells and conserved during this transition, suggesting that they have a key role as early drivers. In addition, recurrent mutations gained in some genes at transformation (for example, PIM1, FRYL and HNF1B) represent cooperating events in the selection of the clones responsible for disease progression. Detailed comparison reveals the gene abnormalities at diagnosis and transformation to be consistent with a branching model of evolution. Finally, the frequent mutation observed in the CD79B gene in this specific subset of patients implies that it is a potential biomarker predicting transformation in WM.

摘要翻译： 

华氏巨球蛋白血症（WM）向弥漫性大B细胞淋巴瘤（DLBCL）的转化见于高达10%的患者，且与不良预后相关。本研究首次对进展为DLBCL的WM患者进行全外显子组测序，并报告可能驱动该过程的遗传学改变。结果表明转化取决于获得性变异的发生频率和特异性，而非其演化时长。我们未在诊断或转化阶段发现共同的突变模式，但在较高比例克隆肿瘤细胞中存在某些异常且在此转化过程中保持稳定，提示其作为早期驱动因素具有关键作用。此外，转化阶段在某些基因中出现的复发性突变（如PIM1、FRYL和HNF1B）代表了疾病进展相关克隆选择中的协同事件。详细比较显示诊断与转化阶段的基因异常符合分支进化模型。最后，在此特定患者亚群中观察到CD79B基因的频繁突变，提示其可作为预测WM转化的潜在生物标志物。

原文链接：

From Waldenström’s macroglobulinemia to aggressive diffuse large B-cell lymphoma: a whole-exome analysis of abnormalities leading to transformation