Somatic variants and frequencies of familial myeloma germline predisposition genes among patients within the CoMMpass dataset.

IF 2.1 4区 医学 Q2 HEMATOLOGY
Erman Akkus, Timur Tuncalı, Hasan Yalim Akin, Meral Beksaç
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引用次数: 0

Abstract

Background: Genetic factors associated with familial multiple myeloma (MM) have been studied, yet the somatic engagement of germline predisposition genes remains underexplored. This study aims to systematically analyze somatic variants in previously reported germline familial myeloma predisposition genes.

Research design and methods: A systematic literature search identified 179 genes associated with familial MM. Somatic variants and associated demographic data from the Multiple Myeloma Research Foundation (MMRF) CoMMpass Study, which includes non-selected myeloma patients (5.3% with a first-degree family history of hematological malignancy) were analyzed.

Results: 1863 somatic variants across the 179 predisposition genes were detected, with substitutions being the most common variant type (95.7%) and missense variants the most frequent consequence (40.6%). Notably mutated genes with pathogenic potential included DIS3, LRP1B, EP300, SAMHD1, ARID1A, DNAH2, MUC17, BIRC6, MYH14, DSP, and DCHS1. Pathogenic variants did not show significant demographic associations. Moreover, variant types, consequences, and associated demographics revealed similar rates in young myeloma patients (≤50 years) and patients with a first-degree family history of hematological malignancy.

Conclusions: This study highlights a significant rate of pathogenic somatic variants in germline predisposition genes of familial myeloma, suggesting candidate genes to be investigated in myelomagenesis.

compass数据集中患者家族性骨髓瘤种系易感性基因的体细胞变异和频率。
背景:与家族性多发性骨髓瘤(MM)相关的遗传因素已被研究,但生殖系易感性基因的体细胞参与仍未得到充分探讨。本研究旨在系统分析先前报道的种系家族性骨髓瘤易感基因的体细胞变异。研究设计和方法:系统的文献检索确定了179个与家族性MM相关的基因。来自多发性骨髓瘤研究基金会(MMRF) CoMMpass研究的体细胞变异和相关人口统计学数据进行了分析,其中包括非选择的骨髓瘤患者(5.3%具有一级血液恶性家族史)。结果:在179个易感基因中检测到1863个体细胞变异,其中替换是最常见的变异类型(95.7%),错义变异是最常见的后果(40.6%)。具有致病潜力的显著突变基因包括DIS3、LRP1B、EP300、SAMHD1、ARID1A、DNAH2、MUC17、BIRC6、MYH14、DSP和DCHS1。致病变异未显示出显著的人口统计学关联。此外,变异类型、后果和相关人口统计数据显示,年轻骨髓瘤患者(≤50岁)和有一级血液恶性家族史的患者的发病率相似。结论:本研究强调家族性骨髓瘤种系易感基因中致病性体细胞变异的显著率,提示骨髓瘤形成中有待研究的候选基因。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
4.70
自引率
3.60%
发文量
98
审稿时长
6-12 weeks
期刊介绍: Advanced molecular research techniques have transformed hematology in recent years. With improved understanding of hematologic diseases, we now have the opportunity to research and evaluate new biological therapies, new drugs and drug combinations, new treatment schedules and novel approaches including stem cell transplantation. We can also expect proteomics, molecular genetics and biomarker research to facilitate new diagnostic approaches and the identification of appropriate therapies. Further advances in our knowledge regarding the formation and function of blood cells and blood-forming tissues should ensue, and it will be a major challenge for hematologists to adopt these new paradigms and develop integrated strategies to define the best possible patient care. Expert Review of Hematology (1747-4086) puts these advances in context and explores how they will translate directly into clinical practice.
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