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.
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.