Background: Approximately 25.0% of metastatic prostate cancer patients harbour DNA damage repair mutations, includingBRCA1andBRCA2, which are actionable targets for poly(ADP-ribose) polymerase (PARP) inhibitors. Accurate detection ofBRCA1/2 mutations is critical for guiding targeted therapies, but crucial pre-analytical factors, such as tissue storage duration and DNA fragmentation, drastically affect the reliability of next-generation sequencing (NGS) using real-world diagnostic specimens. Methods: This multicentre study analysed 954 formalin-fixed paraffin-embedded tissue samples from 11 centres, including 559 biopsies and 395 surgical specimens. This study examined the impact of storage duration (<1 year, 1–2 years, and >2 years) and DNA parameters (concentration and fragmentation index) on NGS success rates. Logistic regression and Cox regression analyses were used to assess correlations between these factors and sequencing outcomes. Results: NGS success rates decreased significantly with longer storage, from 87.8% (<1 year) to 69.1% (>2 years). Samples with higher DNA concentrations and fragmentation indexes had higher success rates (p< 0.001). Surgical specimens had superior success rates (83.3%) compared with biopsies (72.8%) due to better DNA quality. The DNA degradation rate was more pronounced in older samples, underscoring the negative impact of extended storage. Conclusions: Timely testing ofBRCA1/2 mutations is critical for optimizing the identification of prostate cancer patients eligible for PARP inhibitors. Surgical specimens provide more reliable results than biopsies and minimizing the storage duration significantly enhances testing outcomes. Standardizing pre-analytical and laboratory procedures across centres is essential to ensure personalized treatments and improve patient outcomes.
背景：约25.0%的转移性前列腺癌患者携带DNA损伤修复基因突变，包括BRCA1和BRCA2，这些是聚腺苷二磷酸核糖聚合酶（PARP）抑制剂的作用靶点。准确检测BRCA1/2突变对指导靶向治疗至关重要，但关键的分析前因素，如组织存储时间和DNA片段化程度，会显著影响使用真实世界诊断样本进行二代测序（NGS）的可靠性。方法：这项多中心研究分析了来自11个中心的954份福尔马林固定石蜡包埋组织样本，包括559份活检样本和395份手术样本。研究探讨了存储时间（<1年、1-2年和>2年）和DNA参数（浓度和片段化指数）对NGS成功率的影响。采用逻辑回归和Cox回归分析评估这些因素与测序结果之间的相关性。结果：NGS成功率随存储时间延长显著下降，从87.8%（<1年）降至69.1%（>2年）。DNA浓度和片段化指数较高的样本成功率更高（p<0.001）。由于DNA质量更优，手术样本的成功率（83.3%）高于活检样本（72.8%）。DNA降解率在存储时间较长的样本中更为明显，突显了长期存储的负面影响。结论：及时检测BRCA1/2突变对于优化识别适合PARP抑制剂治疗的前列腺癌患者至关重要。手术样本比活检样本提供更可靠的结果，且缩短存储时间可显著提高检测效果。在各中心间标准化分析前和实验室流程对于确保个性化治疗和改善患者预后至关重要。
肿瘤(癌症)患者之家