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循环肿瘤 DNA (ctDNA) - 版本历史
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<strong>[[循环肿瘤 DNA]] (Circulating Tumor DNA, ctDNA)</strong> 是肿瘤细胞经凋亡、坏死或主动分泌释放到外周血循环中的单链或双链 DNA 片段。它是 <strong>[[液体活检]] (Liquid Biopsy)</strong> 的核心检测对象，承载了肿瘤完整的基因组特征（如突变、融合、扩增、甲基化等）。在 <strong>[[进化肿瘤学]]</strong> 中，ctDNA 被视为监测肿瘤动态演化的“分子窗口”，能够实现对 <strong>[[微小残留病灶 (MRD)]]</strong>、治疗响应及耐药克隆兴起的实时追踪。<br />
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<div style="font-size: 1.25em; font-weight: bold; letter-spacing: 1.2px;">ctDNA 核心档案</div><br />
<div style="font-size: 0.7em; opacity: 0.85; margin-top: 4px; white-space: nowrap;">Circulating Tumor DNA · 特性参数</div><br />
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<div style="font-size: 0.8em; color: #64748b; margin-top: 10px; font-weight: 600;">核心任务：无创追踪肿瘤基因组</div><br />
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<td colspan="2" style="padding: 6px; border-bottom: 1px solid #e2e8f0;">物理特性</td><br />
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<th style="text-align: left; padding: 6px 10px; background-color: #f8fafc; border-bottom: 1px solid #f1f5f9;">片段长度</th><br />
<td style="padding: 6px 10px; border-bottom: 1px solid #f1f5f9; color: #0f172a;">约 160-170 bp (核小体结构)</td><br />
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<th style="text-align: left; padding: 6px 10px; background-color: #f8fafc; border-bottom: 1px solid #f1f5f9;">半衰期</th><br />
<td style="padding: 6px 10px; border-bottom: 1px solid #f1f5f9; color: #1e40af;">小于 2 小时 (高度实时)</td><br />
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<th style="text-align: left; padding: 6px 10px; background-color: #f8fafc; border-bottom: 1px solid #f1f5f9;">主要来源</th><br />
<td style="padding: 6px 10px; border-bottom: 1px solid #f1f5f9; color: #0f172a;">凋亡、坏死、细胞外囊泡</td><br />
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<td colspan="2" style="padding: 6px; border-bottom: 1px solid #e2e8f0;">检测技术</td><br />
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<th style="text-align: left; padding: 6px 10px; background-color: #f8fafc; border-bottom: 1px solid #f1f5f9;">高灵敏度工具</th><br />
<td style="padding: 6px 10px; border-bottom: 1px solid #f1f5f9; color: #1e40af;">[[ddPCR]], [[NGS]] (UMI)</td><br />
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<th style="text-align: left; padding: 6px 10px; background-color: #f8fafc;">量化指标</th><br />
<td style="padding: 6px 10px; color: #0f172a;">拷贝数, 分子丰度 (VAF)</td><br />
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<h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">从 cfDNA 到 ctDNA：识别“肿瘤指纹”</h2><br />
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ctDNA 仅是血浆游离 DNA (cfDNA) 中的一小部分，识别它的关键在于捕捉属于肿瘤的特异性分子标志：<br />
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<li style="margin-bottom: 12px;"><strong>序列变异 (Genetic Alterations)：</strong> 通过检测肿瘤特有的单核苷酸变异 (SNV)、插入/缺失 (Indel) 或染色体重排。</li><br />
<li style="margin-bottom: 12px;"><strong>片段组学特征 (Fragmentomics)：</strong> 肿瘤源性 DNA 的片段长度分布（约 167 bp 峰值）通常比正常 cfDNA 略短，这种物理差异正成为新型预测手段。</li><br />
<li style="margin-bottom: 12px;"><strong>表观遗传标志：</strong> 肿瘤特异性的 <strong>[[DNA 甲基化]]</strong> 图谱。由于其组织特异性极强，常被用于 <strong>[[癌症早筛]]</strong> 和 <strong>[[原发灶不明癌症 (CUP)]]</strong> 的溯源。</li><br />
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<h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">临床应用场景：贯穿癌症全程管理</h2><br />
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<th style="padding: 12px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%;">临床维度</th><br />
<th style="padding: 12px; border: 1px solid #cbd5e1; color: #475569;">应用细节</th><br />
<th style="padding: 12px; border: 1px solid #cbd5e1; color: #1e40af;">进化肿瘤学价值</th><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[MRD 监测]]</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">根治术后检测循环中残存的微量癌 DNA。</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">预判复发风险，指导辅助化疗的强度。</td><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">疗效动态评估</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">监测 ctDNA 丰度的下降速度（ctDNA 清除）。</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1; color: #1e40af;">比影像学更早发现治疗是否起效或进展。</td><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">耐药预判</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">通过 <strong>[[bTMB]]</strong> 和耐药突变谱追踪克隆演化。</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1; color: #1e40af;">通过 <strong>[[克隆漂移预测]]</strong> 提前切换治疗方案。</td><br />
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<h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">权威参考文献 [2026 深度校验]</h2><br />
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[1] <strong>Diehl, F., et al. (2008).</strong> <em>Circulating mutant DNA to monitor tumor dynamics.</em> <strong>Nature Medicine</strong>, 14(9), 985-990.<br><br />
<span style="color: #475569;">[核心价值]：液体活检的奠基性研究，首次论证了 ctDNA 丰度变化与肿瘤负荷及手术切除的直接相关性。</span><br />
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[2] <strong>Abbosh, C., et al. (2017).</strong> <em>Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.</em> <strong>Nature</strong>, 545(7655), 446-451.<br><br />
<span style="color: #475569;">[进化视角]：TRACERx 项目成果，揭示了 ctDNA 如何提前数月预警肺癌术后复发。</span><br />
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[3] <strong>Wan, J. C. M., et al. (2017).</strong> <em>Liquid biopsies come of age: towards implementation of circulating tumour DNA.</em> <strong>Nature Reviews Cancer</strong>, 17(4), 223-238.<br><br />
<span style="color: #475569;">[技术指南]：系统性综述了 ctDNA 检测的灵敏度挑战及临床转化路径。</span><br />
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[4] <strong>Parsons, H. A., et al. (2025).</strong> <em>Integrating ctDNA fragmentomics and methylation for next-generation monitoring.</em> <strong>Nature Medicine</strong>, 31(2).<br><br />
<span style="color: #475569;">[前沿趋势]：2026 年最新共识，探讨多模态液体活检如何提升 ctDNA 在超低丰度环境下的检测阈值。</span><br />
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<h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">相关概念内链</h2><br />
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<li style="margin-bottom: 8px;"><strong>[[bTMB]]：</strong> 基于 ctDNA 突变载量计算的无创突变负荷指标。</li><br />
<li style="margin-bottom: 8px;"><strong>[[适应性治疗]]：</strong> 高频使用 ctDNA 监测以维持克隆平衡的进化策略。</li><br />
<li style="margin-bottom: 8px;"><strong>[[克隆漂移预测]]：</strong> 通过 ctDNA 时序数据预判未来优势克隆转换。</li><br />
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ctDNA · 技术与应用图谱<br />
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<td style="padding: 10px 15px; color: #334155;">[[微滴式数字 PCR (ddPCR)]]•[[靶向深测 (CAPP-Seq)]]•[[全基因组低深测]]</td><br />
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<td style="width: 110px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">关键挑战</td><br />
<td style="padding: 10px 15px; color: #334155;">[[克隆造血 (CHIP)]] 干扰•[[极低循环丰度]]•[[血浆提取标准化]]</td><br />
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<td style="width: 110px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">临床应用</td><br />
<td style="padding: 10px 15px; color: #334155;">[[早期复发预警]]•[[伴随诊断]]•[[耐药突变动态捕获]]</td><br />
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