具有有害生殖系DDX41变体的人群的整体癌症风险
Sophia C Korotev1, Jason X Cheng2, Yogameenakshi Haribabu1
1Division of Hematology/Oncology, Department of Medicine, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL 60611.
Haematologica
|February 13, 2025
概括
生殖系DDX41变种可以导致造血性恶性瘤和固体瘤. 建议进行基线骨髓活检,以避免误诊,并建议对那些有癌症家族史的人进行广泛的生殖线检测.
科学领域:
- 遗传学 是一个遗传学.
- 在瘤学瘤学.
- 血液学 血液学 血液学
背景情况:
- 生殖线功能丧失 (LoF) DDX41变体与晚发性造血性恶性瘤 (HMs) 有关,主要是髓状瘤.
- 患有生殖线DDX41LoF变异的个体可能在HM诊断前几年表现出轻度发育不良.
研究的目的:
- 调查与生殖线DDX41LoF变体相关的临床表现和潜在机制.
- 为携带这些变体的个体提供诊断和管理建议.
主要方法:
- 从具有生殖系DDX41LoF变异家族的骨髓活检分析.
- 在队列中评估固体瘤发生率和遗传特征.
- 评估淋巴细胞细胞系和周围血液中的炎症标志物.
主要成果:
- 在患有生殖系DDX41LoF变异的个体的外周血液和骨髓中观察到轻度的发育不良,HM发作之前.
- 到75岁时,固体瘤的显著透,由于没有获得的DDX41突变,建议使用替代机制.
- 在多个固体瘤的家庭中存在额外的生殖系癌症倾向变体.
- 在具有生殖系DDX41LoF变异的个体中,炎症相关蛋白质的差异表达.
结论:
- 对于具有生殖线DDX41LoF等位基因的个体,建议进行基线骨髓活检,以防止骨髓发育综合征过度诊断.
- 生殖系DDX41LoF变体可能通过炎症功能障碍促进实体瘤的发展,可能受到其他癌症倾向基因的影响.
- 广泛的生殖基因检测建议对HMs和个人或家庭固体瘤病史的人进行广泛的生殖基因检测.
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