Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is often the only source of tumor tissue from patients with advanced, inoperable lung cancer. EBUS-TBNA aspirates are used for the diagnosis, staging, and genomic testing to inform therapy options. Here we extracted DNA and RNA from 220 EBUS-TBNA aspirates to evaluate their suitability for whole genome (WGS), whole exome (WES), and comprehensive panel sequencing. For a subset of 40 cases, the same nucleic acid extraction was sequenced using WGS, WES, and the TruSight Oncology 500 assay. Genomic features were compared between sequencing platforms and compared with those reported by clinical testing. A total of 204 aspirates (92.7%) had sufficient DNA (100 ng) for comprehensive panel sequencing, and 109 aspirates (49.5%) had sufficient material for WGS. Comprehensive sequencing platforms detected all seven clinically reported tier 1 actionable mutations, an additional three (7%) tier 1 mutations, six (15%) tier 2–3 mutations, and biomarkers of potential immunotherapy benefit (tumor mutation burden and microsatellite instability). As expected, WGS was more suited for the detection and discovery of emerging novel biomarkers of treatment response. WGS could be performed in half of all EBUS-TBNA aspirates, which points to the enormous potential of EBUS-TBNA as source material for large, well-curated discovery-based studies for novel and more effective predictors of treatment response. Comprehensive panel sequencing is possible in the vast majority of fresh EBUS-TBNA aspirates and enhances the detection of actionable mutations over current clinical testing.
支气管内超声引导下经支气管针吸活检（EBUS-TBNA）通常是晚期不可手术肺癌患者获取肿瘤组织的唯一来源。EBUS-TBNA抽吸物可用于诊断、分期和基因组检测，从而指导治疗方案选择。本研究从220例EBUS-TBNA抽吸物中提取DNA和RNA，评估其是否适用于全基因组测序、全外显子组测序及综合测序组合分析。针对其中40例样本，使用相同核酸提取物分别进行全基因组测序、全外显子组测序及TruSight Oncology 500检测。通过比较不同测序平台的基因组特征，并与临床检测报告进行对照分析，结果显示：204例抽吸物（92.7%）含有足够DNA（100 ng）进行综合测序组合分析，109例（49.5%）具备全基因组测序所需样本量。综合测序平台不仅检测出临床已报告的7个Ⅰ级可干预突变，还额外发现3个（7%）Ⅰ级突变、6个（15%）Ⅱ-Ⅲ级突变，以及可能提示免疫治疗获益的生物标志物（肿瘤突变负荷和微卫星不稳定性）。全基因组测序在检测和发现新型治疗反应生物标志物方面更具优势，该技术可在半数EBUS-TBNA抽吸物中成功实施，表明EBUS-TBNA样本作为高质量研究材料，在大型规范化探索性研究中具有巨大潜力，有助于发现新型且更有效的治疗反应预测因子。绝大多数新鲜EBUS-TBNA抽吸物可进行综合测序组合分析，其检测可干预突变的效能优于当前临床检测方法。
肿瘤(癌症)患者之家