基因条形码揭示了固体和液体活检的克隆构成及其捕捉瘤内异质性的能力
Antonin Serrano1,2,3,4,5,6, Tom S Weber7,8, Jean Berthelet9,10
1Olivia Newton-John Cancer Research Institute, Heidelberg, VIC, 3084, Australia. antonin.serrano@unimelb.edu.au.
Molecular systems biology
|February 11, 2026
概括
乳腺癌中的内异质性 (ITH) 具有挑战性. 在临床前模型中的遗传条形码揭示了克隆多样性差异和可变的DNA脱落,这表明组合活检可以改善ITH评估.
科学领域:
- 在瘤学瘤学.
- 遗传学 遗传学 是一个
- 分子生物学分子生物学
背景情况:
- 内异质性 (ITH) 驱动乳腺癌的进展,转移和治疗耐药性.
- 准确地描述ITH对于预测复发和指导个性化治疗策略至关重要.
研究的目的:
- 通过使用遗传条码,量化比较瘤内克隆组合与针活检和无细胞DNA (cfDNA).
- 评估固体和液体活检作为评估乳腺癌的替代品的实用性.
主要方法:
- 利用遗传条形码来追踪人类乳腺癌克隆的时空组成.
- 分析了六种临床前模型:两种细胞系和四种患者衍生异种移植 (PDX).
- 在初级瘤,针活检和cfDNA中量化比较了克隆组合.
主要成果:
- 克隆多样性在中心明显高于非死核性原发性瘤的外围.
- 在不同模型中,cfDNA流失的差异很大,受瘤负担和亡的影响.
- 结合固体和液体活检的分析,对瘤的克隆组成进行了更为可靠的评估.
结论:
- 在临床前模型中,遗传条形码有效追踪乳腺癌ITH.
- 固体和液体活检为ITH评估提供了补充信息.
- 使用条形码模型的优化活检策略可以改善乳腺癌的临床管理.
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