Thusgaard Christine Fribert, Sadegh Sepideh, Jochumsen Kirsten Marie, Kruse Torben Arvid, Thomassen Mads
Department of Gynecology and Obstetrics, Odense University Hospital, 5000 Odense, Denmark.
Research Unit of Gynecology and Obstetrics, Department of Clinical Research, University of Southern Denmark, Odense University Hospital, 5000 Odense, Denmark.
Int J Mol Sci. 2024 Dec 12;25(24):13349. doi: 10.3390/ijms252413349.
Circulating tumor DNA (ctDNA) is a biomarker that could potentially improve the survival rate of ovarian cancer (OC), e.g., by monitoring treatment response and early relapse detection. However, an optimal method for ctDNA analysis in OC remains to be established. We developed a method for tumor-informed single-nucleotide variant detection of ctDNA in OC using whole-genome sequencing. Tumor and plasma samples obtained at the time of diagnosis from 10 patients with OC were included. The tested method involved applying basic filters with different cut-offs of read depth, allelic depth, and variant allele frequency of tumor and normal DNA. In addition, we applied a new filtering approach using plasma samples from the other included OC patients (the plasma pool) for specific removal of artefacts. The basic filters with varying cut-offs showed minor improvement in signal-to-noise ratio (S2N). However, the addition of the plasma pool filter resulted in a considerable ctDNA signal improvement, indicated by both S2N and z-score. This study demonstrates a promising method for ctDNA detection in OC patients using a tumor-informed approach for whole-genome sequencing. Despite the limited number of patients involved, the results suggest a significant potential of the method for ctDNA signal detection in patients with OC.
循环肿瘤DNA（ctDNA）是一种生物标志物，有可能提高卵巢癌（OC）的生存率，例如通过监测治疗反应和早期复发检测。然而，OC中ctDNA分析的最佳方法仍有待确定。我们开发了一种使用全基因组测序对OC中的ctDNA进行肿瘤信息单核苷酸变异检测的方法。纳入了10例OC患者诊断时获得的肿瘤和血浆样本。测试方法包括应用具有不同肿瘤和正常DNA读取深度、等位基因深度和变异等位基因频率截止值的基本过滤器。此外，我们应用了一种新的过滤方法，使用其他纳入的OC患者的血浆样本（血浆池）来特异性去除伪影。具有不同截止值的基本过滤器在信噪比（S2N）方面显示出轻微改善。然而，添加血浆池过滤器导致ctDNA信号有相当大的改善，这由S2N和z分数表明。本研究展示了一种使用肿瘤信息全基因组测序方法在OC患者中检测ctDNA的有前景的方法。尽管涉及的患者数量有限，但结果表明该方法在OC患者中检测ctDNA信号具有显著潜力。
