Homologous recombination deficiency (HRD) can arise from germline or somatic pathogenic variants as well as other genomic damage and epigenetic alterations in the HR repair pathway. Patients with tumors presenting with an HRD phenotype can show sensitivity to Poly (ADP-ribose) polymerase inhibitors (PARPis). Several promising tests to detect HRD have been developed based on different HRD definitions, biomarkers, and algorithms. However, no consensus on a gold standard HRD test has been established. In this systematic review, a comprehensive list of tests for the detection of HRD was identified and compared regarding HRD definition, biomarkers, and algorithms. PubMed’s Medline and Elsevier’s Embase were systematically searched, resulting in 27 eligible articles meeting the inclusion criteria. The primary challenge when comparing HRD tests lies in the lack of a consensus definition of HRD, as the HRD definition influences the proportion of samples being classified as HRD and impacts the classification performance. This systematic review provides an overview of available HRD tests that can inspire other researchers in searching for a gold standard HRD definition and highlights the importance of the factors that should be considered when choosing an HRD definition and tests for future planning of clinical trials and studies.
同源重组缺陷可由生殖系或体细胞致病性变异以及同源重组修复通路中的其他基因组损伤和表观遗传改变引起。呈现同源重组缺陷表型的肿瘤患者可能对聚腺苷二磷酸核糖聚合酶抑制剂表现出敏感性。基于不同的同源重组缺陷定义、生物标志物和算法，目前已开发出多种具有前景的同源重组缺陷检测方法。然而，关于同源重组缺陷检测的金标准尚未达成共识。本系统性综述通过系统检索PubMed的Medline和Elsevier的Embase数据库，筛选出27篇符合纳入标准的文献，对已识别的同源重组缺陷检测方法进行了全面梳理，并从同源重组缺陷定义、生物标志物和算法角度进行了比较分析。比较不同同源重组缺陷检测方法时面临的主要挑战在于缺乏统一的同源重组缺陷定义共识，因为定义差异直接影响样本被判定为同源重组缺陷的比例，并对分类性能产生显著影响。本综述系统梳理了现有同源重组缺陷检测方法，可为研究者探索金标准同源重组缺陷定义提供参考，并强调了在规划未来临床试验和研究时，选择同源重组缺陷定义及检测方法需重点考量相关因素的重要性。
Homologous Recombination Deficiency Detection Algorithms: A Systematic Review
肿瘤(癌症)患者之家