文章：

基因突变的意义及其对骨髓中偶然发现孤立性del(20q)但无形态学证据表明存在髓系肿瘤患者的预后影响

The significance of genetic mutations and their prognostic impact on patients with incidental finding of isolated del(20q) in bone marrow without morphologic evidence of a myeloid neoplasm

原文发布日期：2020-01-23

DOI: 10.1038/s41408-020-0275-8

类型: Article

开放获取: 是

英文摘要：

Patients with a sole del(20q) chromosomal abnormality and without morphologic features of a myeloid neoplasm (MN) have shown variable clinical outcomes. To explore the potential risk stratification markers in this group of patients, we evaluated their genetic mutational landscape by a 35-gene MN-focused next-generation sequencing (NGS) panel and examined the association of mutations to progression of MNs. Our study included 56 patients over a 10-year period with isolated del(20q), of whom 23 (41.1%) harbored at least one mutation. With a median follow-up of 32.6 months (range: 0.1−159.1), 9 of 23 patients with mutation(s) progressed to MNs, while all 33 patients without mutations did not progress to MN. Kaplan−Meier survival analysis demonstrated the presence of mutation(s) as a significant risk factor for progression to MN (P < 0.0001). MN progression was strongly associated with the presence of non-DNMT3A/TET2/ASXL1 epigenetic modifiers and nonspliceosome mutations (P = 0.003). There was no significant difference among patients with and without MN progression with respect to the number of mutations, variant allele frequency, percentage of del(20q), and other clinical/laboratory variables. This study illustrates the underlying genetic heterogeneity and complexity of isolated del(20q), and underscores the prognostic value of NGS mutational analysis in these cases.
 

摘要翻译： 

仅存在del(20q)染色体异常且无髓系肿瘤形态学特征的患者表现出不同的临床结局。为探索该患者群体中潜在的风险分层标志物，我们通过35基因髓系肿瘤靶向二代测序面板评估了其基因突变谱，并检验了突变与髓系肿瘤进展的关联。本研究纳入了10年间56例孤立性del(20q)患者，其中23例（41.1%）携带至少一种突变。在中位随访32.6个月（范围：0.1-159.1）期间，23例携带突变患者中有9例进展为髓系肿瘤，而所有33例无突变患者均未发生髓系肿瘤进展。Kaplan-Meier生存分析显示突变存在是进展为髓系肿瘤的重要风险因素（P < 0.0001）。髓系肿瘤进展与携带非DNMT3A/TET2/ASXL1表观遗传修饰因子及非剪接体突变显著相关（P = 0.003）。在突变数量、变异等位基因频率、del(20q)百分比及其他临床/实验室变量方面，进展与非进展患者之间无显著差异。本研究揭示了孤立性del(20q)潜在的遗传异质性和复杂性，并强调了二代测序突变分析在此类病例中的预后价值。

原文链接：

The significance of genetic mutations and their prognostic impact on patients with incidental finding of isolated del(20q) in bone marrow without morphologic evidence of a myeloid neoplasm