获得足够的胰胆管肿瘤组织进行基因组分析存在局限性。使用血浆进行液体活检并不能提供足够的敏感性。因此，本研究旨在确定胆汁和血浆之间液体活检在识别致癌和匹配药物突变方面的有效性。本研究创建了一个特定于胰胆管癌(PBCA)的60个显著突变基因面板，并用它对212个脱氧核糖核酸(DNA)样本（87个胆汁上清、87个胆汁沉淀和38个血浆）进行基因组分析，这些样本来自于87例患有PBCA的患者。比较了从胆汁和血浆中提取的DNA量以及38对PBCA患者的胆汁和血浆的基因组分析结果。最后，我们对87个胆汁和38个血浆样本进行了药物突变检测能力的研究。 血浆中的DNA量显著低于胆汁（p < 0.001）。在38个患者中，胆汁样本中鉴定出了21个患者（55％）的致癌突变和9个患者（24％）的血浆样本中（p = 0.005）。胆汁在识别可用药物治疗的突变方面比血浆更为敏感（p = 0.032）。本文作者发现，在联合胆汁和血浆中检测到了23个匹配的药物突变，其中包括5个ERBB2、4个ATM、3个BRAF、3个BRCA2、3个NF1、2个PIK3CA、1个BRCA1、1个IDH1和1个PALB2。 使用胆汁进行液体活检可能有助于寻找治疗药物，并利用所获得的基因组信息可以改善PBCA患者的预后。甲醛固定石蜡包埋组织的基因组分析可能为分子和免疫肿瘤学治疗提供可操作的靶点。但大多数胰胆管恶性肿瘤是不可切除的，无法获得甲醛固定石蜡包埋组织。尽管最近几年已经使用了使用血浆的全面基因组分析测试，但是使用胆汁的效用尚不清楚。我们的研究揭示了在晚期PBCA患者中，胆汁比血浆识别出更多可用药物治疗的突变。胆汁可以帮助扩大受益于靶向药物的患者人群。 ©2023美国癌症协会。

Obtaining sufficient pancreaticobiliary tumor tissue for genomic profiling has limitations. Liquid biopsies using plasma do not provide sufficient sensitivity. Thus, this study aimed to determine the effectiveness of liquid biopsy between bile and plasma for identifying oncogenic and drug-matched mutations.This study created a panel of 60 significantly mutated genes specific to pancreaticobiliary cancer (PBCA) and used it for genomic analysis of 212 deoxyribonucleic acid (DNA) samples (87 bile supernatant, 87 bile precipitate, and 38 plasma) from 87 patients with PBCA. The quantity of extracted DNA from bile and plasma was compared, as were genomic profiles of 38 pairs of bile and plasma from 38 patients with PBCA. Finally, we investigated 87 bile and 38 plasma for the ability to detect druggable mutations.The amount of DNA was significantly lower in plasma than in bile (p < .001). Oncogenic mutations were identified in 21 of 38 (55%) patients in bile and nine (24%) in plasma samples (p = .005). Bile was significantly more sensitive than plasma in identifying druggable mutations (p = .032). The authors detected 23 drug-matched mutations in combined bile and plasma, including five ERBB2, four ATM, three BRAF, three BRCA2, three NF1, two PIK3CA, one BRCA1, one IDH1, and one PALB2.Liquid biopsy using bile may be useful in searching for therapeutic agents, and using the obtained genomic information may improve the prognoses of patients with PBCA.Genomic profiling of formalin-fixed paraffin-embedded tissues may provide actionable targets for molecular and immuno-oncological treatment. However, most pancreaticobiliary malignancies are unresectable and formalin-fixed paraffin-embedded tissues cannot be obtained. Although comprehensive genomic profiling tests using plasma have been used in recent years, the utility of those using bile is not clear. Our study revealed that bile identified more drug-matched mutations than plasma in advanced pancreaticobiliary cancer patients. Bile may help widen the patient population benefiting from targeted drugs.© 2023 American Cancer Society.