循环肿瘤DNA在恶性原发性骨肿瘤诊疗中的临床应用与研究进展

doi:10.3969/j.issn.1004-583X.2026.08.013

摘要/Abstract

摘要：

恶性原发性骨肿瘤好发于儿童及青少年,恶性程度高、预后差,传统组织活检存在有创性、空间异质性、无法动态监测等诸多局限性。循环肿瘤DNA作为液体活检的核心标志物,携带肿瘤特异性基因组与表观遗传学异常,为骨肿瘤的精准诊疗提供了全新方向。本文就循环肿瘤DNA在恶性原发性骨肿瘤中的生物学基础、检测技术规范、临床应用现状、多模态联合检测策略及现存挑战与未来发展方向进行系统综述,旨在为其临床转化与常规应用提供理论依据与实践参考。

关键词: 骨肉瘤, 循环肿瘤DNA, 恶性原发性骨肿瘤, 尤文肉瘤, 软骨肉瘤, 液体活检

中图分类号:

R738.1

王安琪, 吕美琼, 徐颖, 唐嘉, 张孝闽, 杨静雯. 循环肿瘤DNA在恶性原发性骨肿瘤诊疗中的临床应用与研究进展[J]. 临床荟萃, 2026, 41(8): 747-753.

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链接本文: https://www.lchc.cn/CN/10.3969/j.issn.1004-583X.2026.08.013

https://www.lchc.cn/CN/Y2026/V41/I8/747

图/表 2

参考文献 57

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检测技术	最低检测限	核心检测范围	最低cfDNA 需求量	实验室间一致性	核心临床应用场景	主要优势	主要局限性
ddPCR	0.01% VAF	预设热点突变、融合基因	1~5 ng	95% (VAF<0.5%)	MRD监测、疗效动态监测、已知靶点随访	敏感度高、重复性好、成本低、检测周期短	仅能检测已知位点,无法发现新发基因组变异
杂交捕获靶向 NGS	0.1% VAF	单核苷酸变异、InDel、CNA、融合基因、结构变异	≥20 ng	78% (VAF<0.5%)	初诊基因分型、耐药机制解析、克隆演化监测	可全景分析肿瘤基因组,发现新发驱动变异	对样本量要求高,成本较高,生物信息分析流程复杂
低深度全基因组测序	10% CNA阈值	全基因组CNA	5~10 ng	85%~90%	初诊拷贝数谱分析、组织样本不足时的替代分型	样本需求量低,可全基因组CNA分析	无法检测点突变与融合基因,对低肿瘤分数样本敏感度低

检测技术	最低检测限	核心检测范围	最低cfDNA 需求量	实验室间一致性	核心临床应用场景	主要优势	主要局限性
ddPCR	0.01% VAF	预设热点突变、融合基因	1~5 ng	95% (VAF<0.5%)	MRD监测、疗效动态监测、已知靶点随访	敏感度高、重复性好、成本低、检测周期短	仅能检测已知位点,无法发现新发基因组变异
杂交捕获靶向 NGS	0.1% VAF	单核苷酸变异、InDel、CNA、融合基因、结构变异	≥20 ng	78% (VAF<0.5%)	初诊基因分型、耐药机制解析、克隆演化监测	可全景分析肿瘤基因组,发现新发驱动变异	对样本量要求高,成本较高,生物信息分析流程复杂
低深度全基因组测序	10% CNA阈值	全基因组CNA	5~10 ng	85%~90%	初诊拷贝数谱分析、组织样本不足时的替代分型	样本需求量低,可全基因组CNA分析	无法检测点突变与融合基因,对低肿瘤分数样本敏感度低

循环肿瘤DNA在恶性原发性骨肿瘤诊疗中的临床应用与研究进展

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