文章：

在多发性骨髓瘤复发时，双等位基因失活更为常见，这表明RB1是一个独立的预后标志物

Bi-allelic inactivation is more prevalent at relapse in multiple myeloma, identifying RB1 as an independent prognostic marker

原文发布日期：2017-02-24

DOI: 10.1038/bcj.2017.12

类型: Original Article

开放获取: 是

英文摘要：

The purpose of this study is to identify prognostic markers and treatment targets using a clinically certified sequencing panel in multiple myeloma. We performed targeted sequencing of 578 individuals with plasma cell neoplasms using the FoundationOne Heme panel and identified clinically relevant abnormalities and novel prognostic markers. Mutational burden was associated with maf and proliferation gene expression groups, and a high-mutational burden was associated with a poor prognosis. We identified homozygous deletions that were present in multiple myeloma within key genes, including CDKN2C, RB1, TRAF3, BIRC3 and TP53, and that bi-allelic inactivation was significantly enriched at relapse. Alterations in CDKN2C, TP53, RB1 and the t(4;14) were associated with poor prognosis. Alterations in RB1 were predominantly homozygous deletions and were associated with relapse and a poor prognosis which was independent of other genetic markers, including t(4;14), after multivariate analysis. Bi-allelic inactivation of key tumor suppressor genes in myeloma was enriched at relapse, especially in RB1, CDKN2C and TP53 where they have prognostic significance.

摘要翻译： 

本研究旨在通过临床认证的测序 panel 在多发性骨髓瘤中寻找预后标志物和治疗靶点。我们采用FoundationOne Heme panel对578例浆细胞肿瘤患者进行靶向测序，识别出临床相关异常及新型预后标志物。突变负荷与MAF及增殖基因表达群组相关，高突变负荷与不良预后相关。我们在多发性骨髓瘤关键基因（包括CDKN2C、RB1、TRAF3、BIRC3和TP53）中发现纯合性缺失，且双等位基因失活在复发样本中显著富集。CDKN2C、TP53、RB1及t(4;14)的变异与不良预后相关。RB1变异主要为纯合性缺失，与复发和不良预后相关，经多变量分析显示该关联独立于t(4;14)等其他遗传标志物。骨髓瘤关键抑癌基因的双等位基因失活在复发样本中富集，尤其在RB1、CDKN2C和TP53中具有预后意义。

原文链接：

Bi-allelic inactivation is more prevalent at relapse in multiple myeloma, identifying RB1 as an independent prognostic marker