From Waldenström's macroglobulinemia to aggressive diffuse large B-cell lymphoma: a whole-exome analysis of abnormalities leading to transformation.
From Waldenström's macroglobulinemia to aggressive diffuse large B-cell lymphoma: a whole-exome analysis of abnormalities leading to transformation.
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DOI：
10.1038/bcj.2017.72
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发表时间：
2017-08-25
影响因子：
12.8
通讯作者：
García-Sanz R
中科院分区：
文献类型：
--
作者：
Jiménez C;Alonso-Álvarez S;Alcoceba M;Ordóñez GR;García-Álvarez M;Prieto-Conde MI;Chillón MC;Balanzategui A;Corral R;Marín LA;Gutiérrez NC;Puig N;Sarasquete ME;González M;García-Sanz R
高达 10% 的患者会发生华氏巨球蛋白血症 (WM) 向弥漫性大 B 细胞淋巴瘤 (DLBCL) 的转变，并且与不良后果相关。在这里，我们对进化为 DLBCL 的 WM 患者进行了首次全外显子组测序研究，并报告了可能驱动这一过程的基因改变。我们的结果表明，转化取决于获得性变异的频率和特异性，而不是其进化的持续时间。我们在诊断或转化时没有发现常见的突变模式；然而，在这一转变过程中，高比例的克隆肿瘤细胞中存在并保守的某些异常现象，表明它们作为早期驱动因素发挥着关键作用。此外，一些基因在转化过程中获得的反复突变（例如 PIM1、FRYL 和 HNF1B）代表了选择负责疾病进展的克隆的协同事件。详细的比较揭示了诊断和转化时的基因异常与进化的分支模型一致。最后，在这一特定患者亚群中观察到的 CD79B 基因频繁突变意味着它是预测 WM 转化的潜在生物标志物。
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.
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