Department of Lymphoma and Myeloma and.
Department of Biostatistics, MD Anderson Cancer Center, University of Texas, Houston, TX.
Blood Adv. 2020 Jul 14;4(13):2927-2938. doi: 10.1182/bloodadvances.2019001350.
Mantle cell lymphoma (MCL) is an incurable rare subtype of non-Hodgkin lymphoma and is subject to relapse and therapeutic resistance. Molecular aberrations in MCL affect pathogenesis, prognosis, and therapeutic response. In this systematic review, we searched 3 databases and selected 32 articles that described mutations in MCL patients. We then conducted a meta-analysis using a Bayesian multiregression model to analyze patient-level data in 2127 MCL patients, including prevalence of mutations. In tumor or bone marrow samples taken at diagnosis or baseline, ATM was the most frequently mutated gene (43.5%) followed by TP53 (26.8%), CDKN2A (23.9%), and CCND1 (20.2%). Aberrations were also detected in IGH (38.4%) and MYC (20.8%), primarily through cytogenetic methods. Other common baseline mutations were NSD2 (15.0%), KMT2A (8.9%), S1PR1 (8.6%), and CARD11 (8.5%). Our data also show a change in mutational status from baseline samples to samples at disease progression and present mutations of interest in MCL that should be considered for future analysis. The genes with the highest mutational frequency difference (>5%) are TP53, ATM, KMT2A, MAP3K14, BTK, TRAF2, CHD2, TLR2, ARID2, RIMS2, NOTCH2, TET2, SPEN, NSD2, CARD11, CCND1, SP140, CDKN2A, and S1PR1. These findings provide a summary of the mutational landscape of MCL. The genes with the highest change in mutation frequency should be included in targeted next-generation sequencing panels for future studies. These findings also highlight the need for analysis of serial samples in MCL. Patient-level data of prevalent mutations in MCL provide additional evidence emphasizing molecular variability in advancing precision medicine initiatives in MCL.
套细胞淋巴瘤（MCL）是一种无法治愈的罕见非霍奇金淋巴瘤亚型，容易复发和产生治疗抵抗。MCL 的分子异常影响发病机制、预后和治疗反应。在这项系统评价中，我们检索了 3 个数据库，筛选了 32 篇描述 MCL 患者突变的文章。然后，我们使用贝叶斯多回归模型对 2127 例 MCL 患者的患者水平数据进行了荟萃分析，包括突变的流行率。在诊断或基线时采集的肿瘤或骨髓样本中，ATM 是最常突变的基因（43.5%），其次是 TP53（26.8%）、CDKN2A（23.9%）和 CCND1（20.2%）。IGH（38.4%）和 MYC（20.8%）也检测到异常，主要通过细胞遗传学方法。其他常见的基线突变是 NSD2（15.0%）、KMT2A（8.9%）、S1PR1（8.6%）和 CARD11（8.5%）。我们的数据还显示，基线样本和疾病进展时样本的突变状态发生了变化，并提出了 MCL 中应考虑用于未来分析的感兴趣突变。突变频率差异>5%的基因是 TP53、ATM、KMT2A、MAP3K14、BTK、TRAF2、CHD2、TLR2、ARID2、RIMS2、NOTCH2、TET2、SPEN、NSD2、CARD11、CCND1、SP140、CDKN2A 和 S1PR1。这些发现提供了 MCL 突变景观的概述。突变频率变化最大的基因应包含在下一代靶向测序面板中，用于未来的研究。这些发现还强调了在 MCL 中分析连续样本的必要性。MCL 中常见突变的患者水平数据提供了额外的证据，强调了在推进 MCL 精准医学计划中分子变异性的重要性。
