靶向治疗的出现改变了卵巢癌的治疗。然而，精准医学的生物标志物分析受到高质量、富含肿瘤的组织样本的限制。在腹水中使用游离 DNA (cfDNA) 为这一挑战提供了一个潜在的解决方案。在这项研究中，对腹水来源的 cfDNA 样本（来自 15 名卵巢癌患者的 26 个样本）进行了新一代测序，其中匹配的 DNA 来自腹水来源的肿瘤细胞 (n = 5) 并存档福尔马林固定石蜡包埋(FFPE) 组织 (n = 5)。与 FFPE 和腹水细胞 DNA 相比，cfDNA 实现了类似的肿瘤纯度和变异检测。对大规模基因组改变、杂合性丧失和肿瘤突变负担的分析发现了 6 例高度基因组不稳定性的病例（其中 4 例具有致病性 BRCA1 和 BRCA2 突变）。连续腹水样本之间的拷贝数谱和亚克隆患病率发生变化，特别是在 Chr17p13.1 和 Chr8q 中的缺失和染色体碎裂导致临床相关 TP53 和 MYC 变异随时间变化的情况下。腹水 cfDNA 识别出临床上可操作的信息，与组织活检一致，从而实现机会性分子分析。这提倡分析腹水 cfDNA，而不是通过活检获取肿瘤组织。© 2024 作者。约翰·威利出版的《分子肿瘤学》

The emergence of targeted therapies has transformed ovarian cancer treatment. However, biomarker profiling for precision medicine is limited by access to quality, tumour-enriched tissue samples. The use of cell-free DNA (cfDNA) in ascites presents a potential solution to this challenge. In this study, next-generation sequencing was performed on ascites-derived cfDNA samples (26 samples from 15 human participants with ovarian cancer), with matched DNA from ascites-derived tumour cells (n = 5) and archived formalin-fixed paraffin-embedded (FFPE) tissue (n = 5). Similar tumour purity and variant detection were achieved with cfDNA compared to FFPE and ascites cell DNA. Analysis of large-scale genomic alterations, loss of heterozygosity and tumour mutation burden identified six cases of high genomic instability (including four with pathogenic BRCA1 and BRCA2 mutations). Copy number profiles and subclone prevalence changed between sequential ascites samples, particularly in a case where deletions and chromothripsis in Chr17p13.1 and Chr8q resulted in changes in clinically relevant TP53 and MYC variants over time. Ascites cfDNA identified clinically actionable information, concordant to tissue biopsies, enabling opportunistic molecular profiling. This advocates for analysis of ascites cfDNA in lieu of accessing tumour tissue via biopsy.© 2024 The Author(s). Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.