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直接HRD允许基于痕的敏感分类同类重组缺陷的同类重组缺陷

Ruolin Liu¹, Eugenia Roberts¹, Heather A Parsons²

¹Broad Institute of MIT and Harvard, Cambridge, MA, 02142, United States.

Nucleic acids research

|April 23, 2025

概括

DirectHRD是一种新的基于基因组痕的分类器,可以准确地检测癌症中的同源重组缺陷 (HRD). 这种全基因组测序方法在液体活检中显示出高灵敏度,改善了针对个性化癌症治疗的HRD检测.

科学领域:

基因组学就是基因组学.
癌症生物学癌症生物学
生物标志物发现发现

背景情况:

同源重组缺陷 (HRD) 是PARP抑制剂和化疗疗效能的关键生物标志物.
目前的HRD检测方法在敏感性方面扎,特别是在液体活检等低纯度样本中.
基因组痕表明HRD,导致FDA批准了基于痕的测试.

研究的目的:

开发和验证DirectHRD,一种基于基因组痕的新型分类器,用于使用全基因组测序 (WGS) 检测HRD.
评估DirectHRD在多种癌症类型的瘤和无细胞DNA (cfDNA) 样本中的灵敏度和特异性.
将DirectHRD的性能与现有的基于WGS的HRD检测方法进行比较.

主要方法:

直接HRD使用微同源的小删除作为特定的HRD痕在概率框架内.
该分类器应用于501个瘤活检和90个来自乳腺,卵巢,前列腺和胰腺癌的cfDNA样本.
使用诸如cfDNA的检测率,特异性和曲线下的面积 (AUC) 等指标来评估性能.

主要成果:

在501个瘤活检中,DirectHRD实现了100%的HRD检测,特异性超过90%.
在90个cfDNA样本中,DirectHRD显示AUC为0.87.
该方法检测到cfDNA中瘤分数低至1%的HRD,显示出比当前方法高出10倍的灵敏度.

结论:

DirectHRD提供了一种高度敏感和特定的方法,用于使用WGS检测HRD.
它在低分数cfDNA中检测HRD的能力是液体活检应用的重大进步.
直接HRD有可能改善针对癌症治疗的患者选择.

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