Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Br J Haematol. 2021 Jun;193(5):867-881. doi: 10.1111/bjh.17251. Epub 2021 Feb 7.
Circulating tumour DNA (ctDNA) is a highly versatile analyte and an emerging biomarker for detection of tumour-specific sequences in lymphoid malignancies. Since ctDNA is derived from tumour cells throughout the body, it overcomes fundamental limitations of tissue biopsies by capturing the complete molecular profile of tumours, including those from inaccessible anatomic locations. Assays for ctDNA are minimally invasive and serial sampling monitors the effectiveness of therapy and identifies minimal residual disease below the detection limit of standard imaging scans. Dynamic changes in ctDNA levels measure real-time tumour kinetics, and early reductions in ctDNA during treatment correlate with clinical outcomes in multiple B-cell lymphomas. After therapy, ctDNA can effectively discriminate between patients who achieved a complete molecular remission from those with residual treatment-resistant disease. Serial monitoring of ctDNA after therapy can detect early molecular relapse and identify drug-resistant clones that harbour targetable mutations. In order for ctDNA to reach its full potential, the standardization and harmonization of the optimal pre-analytical and analytical techniques for B-cell lymphomas is a critically necessary requirement. Prospective validation of ctDNA within clinical studies is also required to determine its clinical utility as an adjunctive decision-making tool.
循环肿瘤 DNA（ctDNA）是一种非常灵活的分析物，也是检测淋巴恶性肿瘤中肿瘤特异性序列的新兴生物标志物。由于 ctDNA 源自全身的肿瘤细胞，因此它克服了组织活检的基本局限性，可捕获肿瘤的完整分子谱，包括那些来自难以到达的解剖位置的肿瘤。ctDNA 检测方法微创，连续采样可监测治疗效果，并在标准成像扫描的检测限以下识别微小残留疾病。ctDNA 水平的动态变化可测量实时肿瘤动力学，治疗过程中 ctDNA 的早期减少与多种 B 细胞淋巴瘤的临床结局相关。治疗后，ctDNA 可有效区分达到完全分子缓解的患者和仍有残留治疗耐药性疾病的患者。治疗后连续监测 ctDNA 可检测早期分子复发，并识别携带可靶向突变的耐药克隆。为了充分发挥 ctDNA 的潜力，标准化和协调 B 细胞淋巴瘤的最佳分析前和分析技术是至关重要的要求。还需要在临床研究中对 ctDNA 进行前瞻性验证，以确定其作为辅助决策工具的临床效用。
