Vanderstichele Adriaan, Busschaert Pieter, Landolfo Chiara, Olbrecht Siel, Coosemans An, Froyman Wouter, Loverix Liselore, Concin Nicole, Braicu Elena Ioana, Wimberger Pauline, Van Nieuwenhuysen Els, Han Sileny N, Van Gorp Toon, Venken Tom, Heremans Ruben, Neven Patrick, Bourne Tom, Van Calster Ben, Timmerman Dirk, Lambrechts Diether, Vergote Ignace
Department of Obstetrics and Gynaecology, University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium.
Department of Oncology, KU Leuven, Gynaecological Oncology, University Hospitals Leuven, Leuven, Belgium.
NPJ Genom Med. 2022 Apr 28;7(1):30. doi: 10.1038/s41525-022-00300-5.
Fragmentation patterns of plasma cell-free DNA (cfDNA) are known to reflect nucleosome positions of cell types contributing to cfDNA. Based on cfDNA fragmentation patterns, the deviation in nucleosome footprints was quantified between diagnosed ovarian cancer patients and healthy individuals. Multinomial modeling was subsequently applied to capture these deviations in a per sample nucleosome footprint score. Validation was performed in 271 cfDNAs pre-surgically collected from women with an adnexal mass. We confirmed that nucleosome scores were elevated in invasive carcinoma patients, but not in patients with benign or borderline disease. Combining nucleosome scores with chromosomal instability scores assessed in the same cfDNA improved prediction of malignancy. Nucleosome scores were, however, more reliable to predict non-high-grade serous ovarian tumors, which are characterized by low chromosomal instability. These data highlight that compared to chromosomal instability, nucleosome footprinting provides a complementary and more generic read-out for pre-surgical diagnosis of invasive disease in women with adnexal masses.
已知浆细胞游离DNA（cfDNA）的片段化模式可反映对cfDNA有贡献的细胞类型的核小体位置。基于cfDNA片段化模式，对确诊的卵巢癌患者和健康个体之间核小体足迹的偏差进行了量化。随后应用多项模型来获取每个样本核小体足迹评分中的这些偏差。对从附件包块女性患者术前收集的271份cfDNA进行了验证。我们证实，浸润性癌患者的核小体评分升高，但良性或交界性疾病患者的核小体评分未升高。将核小体评分与在相同cfDNA中评估的染色体不稳定性评分相结合，可改善对恶性肿瘤的预测。然而，核小体评分对于预测非高级别浆液性卵巢肿瘤更可靠，这些肿瘤的特征是染色体不稳定性低。这些数据表明，与染色体不稳定性相比，核小体足迹分析为附件包块女性患者术前诊断浸润性疾病提供了一种互补且更通用的指标。
