文章：

套细胞淋巴瘤的基因组图谱和预后分析

Genomic landscape and prognostic analysis of mantle cell lymphoma

原文发布日期：2018-05-14 

英文摘要：

To gain insight into the molecular pathogenesis of patients with mantle cell lymphoma (MCL), next-generation whole-exome sequencing of 16 MCL patients was performed. We identified recurrent mutations in genes that are well known to be functionally relevant in MCL, including ATM (37.5%), TP53 (31.3%), WHSC1 (31.3%), CCND1 (18.8%), NOTCH2 (6.3%), and CDKN2A (6.3%). We also identified somatic mutations in genes for which a functional role in MCL has not been previously suspected. These genes included CCDC15, APC, CDH1, S1PR1, ATRX, BRCA2, CASP8, and NOTCH3. Further, we investigated the prognostic factors associated with MCL from clinical, pathological, and genetic mutations. Mutations of TP53 (P = 0.021) was a significant prognostic factor with shorter overall survival (OS). Although there was no statistical difference, the median survival time of patients with WHSC1 mutations was shorter than those without mutations (P = 0.070). Mutations in ATM and CCND1 had no prognostic value (P = 0.552, 0.566). When adjusted for MCL International Prognostic Index (MIPI) or combined MCL-International Prognostic Index (MIPI-c), TP53 and WHSC1 mutations were the most important prognostic factors in MCL (P < 0.05). Our data provide an unbiased view of the landscape of mutations in MCL and commend that all patients benefit from mutations of TP53 and WHSC1 at diagnosis, in addition to MIPI and MIPI-c score. 

摘要翻译： 

为深入探究套细胞淋巴瘤（MCL）患者的分子发病机制，我们对16例MCL患者进行了新一代全外显子组测序。研究发现存在与MCL功能密切相关的复发性基因突变，包括ATM（37.5%）、TP53（31.3%）、WHSC1（31.3%）、CCND1（18.8%）、NOTCH2（6.3%）和CDKN2A（6.3%）。同时我们还发现了既往未认为与MCL存在功能关联的体细胞突变基因，包括CCDC15、APC、CDH1、S1PR1、ATRX、BRCA2、CASP8和NOTCH3。此外，我们从临床、病理及基因突变角度分析了MCL的预后相关因素：TP53突变（P=0.021）是导致总生存期（OS）缩短的重要预后因素；尽管未达统计学差异，但WHSC1突变患者的中位生存时间较无突变者更短（P=0.070）；ATM与CCND1突变则无预后价值（P=0.552，0.566）。经MCL国际预后指数（MIPI）或联合MCL国际预后指数（MIPI-c）校正后，TP53与WHSC1突变成为MCL最重要的预后因素（P<0.05）。本研究数据提供了MCL突变谱的客观视角，表明所有患者除参考MIPI和MIPI-c评分外，还应从诊断阶段即关注TP53与WHSC1突变带来的临床影响。

原文链接：

Genomic landscape and prognostic analysis of mantle cell lymphoma