Department of Hematology, University Hospital Kralovske Vinohrady, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
BIOCEV, First Faculty of Medicine, Charles University, Prumyslova 595, 25250, Vestec, Czech Republic.
Ann Hematol. 2022 Nov;101(11):2393-2403. doi: 10.1007/s00277-022-04949-x. Epub 2022 Sep 8.
Somatic mutations of genes involved in NF-κB, PI3K/AKT, NOTCH, and JAK/STAT signaling pathways play an important role in the pathogenesis of Hodgkin lymphoma (HL). HL tumor cells form only about 5% of the tumor mass; however, it was shown that HL tumor-derived DNA could be detected in the bloodstream. This circulating tumor DNA (ctDNA) reflects the genetic profile of HL tumor cells and can be used for qualitative and quantitative analysis of tumor-specific somatic DNA mutations within the concept of liquid biopsy. Overall, the most frequently mutated gene in HL is STAT6; however, the exact spectrum of mutations differs between individual HL histological subtypes. Importantly, reduction of ctDNA plasma levels after initial treatment is highly correlated with prognosis. Therefore, ctDNA shows great promise as a novel tool for non-invasive tumor genome analysis for biomarker driven therapy as well as for superior minimal residual disease monitoring and treatment resistance detection. Here, we summarize the recent advancements of ctDNA analysis in HL with focus on ctDNA detection methodologies, genetic profiling of HL and its clonal evolution, and the emerging prognostic value of ctDNA.
参与 NF-κB、PI3K/AKT、NOTCH 和 JAK/STAT 信号通路的基因的体细胞突变在霍奇金淋巴瘤（HL）的发病机制中发挥重要作用。HL 肿瘤细胞仅形成肿瘤团块的约 5%；然而，已经表明可以在血液中检测到 HL 肿瘤衍生的 DNA。这种循环肿瘤 DNA（ctDNA）反映了 HL 肿瘤细胞的遗传特征，并可用于在液体活检概念中对肿瘤特异性体细胞 DNA 突变进行定性和定量分析。总体而言，HL 中最常突变的基因是 STAT6；然而，个别 HL 组织学亚型之间的突变谱确实存在差异。重要的是，初始治疗后 ctDNA 血浆水平的降低与预后高度相关。因此，ctDNA 有望成为一种新型工具，用于基于生物标志物的治疗进行非侵入性肿瘤基因组分析，以及用于更优的微小残留病监测和治疗耐药性检测。在这里，我们总结了 ctDNA 分析在 HL 中的最新进展，重点介绍了 ctDNA 检测方法、HL 的遗传特征及其克隆演变，以及 ctDNA 新兴的预后价值。
