A blood-based approach such as circulating tumor DNA remains challenging in diagnosis for early-stage disease. Bronchial washing (BW) is a minimally invasive procedure that yields fluids that may contain tumor DNA. Therefore, we prospectively enrolled 12 patients with early-stage non-small cell lung cancer without endoscopically visible tumors. Somatic mutations were analyzed using ultra-deep next-generation sequencing in 48 paired specimens (primary tumor tissue, normal tissue, BW supernatant, and BW precipitate). In primary tumors, 130 missense mutations/indels (5-16 per patient) and 20 driver mutations (0-3 per patient) were found. Concordance of driver mutations between BW fluids and primary tumors was 95.0%. The allele frequencies for missense mutations/indels in BW supernatants significantly correlated with those in primary tumors and were higher than those in BW precipitates. These findings suggest that BW supernatants are reflective of tumor-associated mutations and could be used for early-stage lung cancer diagnosis.
摘要
早期疾病的诊断中，难以采用循环肿瘤 DNA 等以血液为基础的诊断方法。支气管冲洗 (BW) 是一种微创手术，可产生可能含有肿瘤 DNA 的冲洗液。因此，本研究前瞻性分析了 12 例内镜下无可见肿瘤的早期非小细胞肺癌患者临床资料。采用超深新一代测序技术对 48 对标本(原发肿瘤组织、正常组织、BW 上清液和 BW 沉淀物)进行了体细胞突变分析。在原发性肿瘤中，发现 130 处错义突变/插入缺失(每位患者 5‐16 处)和 20 处驱动突变(每位患者 0‐3处)。BW 液与原发肿瘤的驱动突变一致性为 95.0%。BW 上清液中错义突变/插入缺失的等位基因频率与原发肿瘤的等位基因频率显著相关，且高于 BW 沉淀物。结果表明，BW 上清液可反映出肿瘤相关突变，可用于早期肺癌的诊断。
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