导管内乳头状粘液性肿瘤（IPMN）是胰腺癌的潜在前驱病变。我们使用数字液滴聚合酶链式反应 (ddPCR) 和循环上皮细胞 (CEC) 评估了筛查无细胞 DNA (cfDNA) 中 KRAS 原癌基因、GTPase (KRAS) 和 GNAS 复合位点 (GNAS) 突变的功效检测作为 IPMN 患者风险分层的生物标志物。我们前瞻性地收集了 25 名有恶性进展风险的切除患者和 23 名接受临床监测的患者的血浆样本。我们的研究结果显示，在整个队列中，KRAS 突变占 10.4%，GNAS 突变占 18.8%。在切除的 IPMN 患者中，KRAS 和 GNAS 突变检出率分别为 16.0% 和 32.0%，而在保守治疗的 IPMN 中，两者的检出率均为 4.0%。与监测下的 IPMN 相比，切除的 IPMN 中 cfDNA 中的 GNAS 突变显着更普遍 (P = 0.024)。未检测到 CEC。 KRAS 和 GNAS 突变的缺失可能是分支导管 IPMN 的可靠标志，且没有令人担忧的特征。 GNAS 突变的出现可能会促使影像监测得到加强。无论是已确定的令人担忧的特征的存在，还是 GNAS 或 KRAS 突变，似乎都无法有效识别 IPMN 患者的重度不典型增生。© 2024 作者。约翰·威利出版的《分子肿瘤学》

Intraductal papillary mucinous neoplasms (IPMNs) are potential precursor lesions of pancreatic cancer. We assessed the efficacy of screening for KRAS proto-oncogene, GTPase (KRAS), and GNAS complex locus (GNAS) mutations in cell-free DNA (cfDNA)-using digital droplet polymerase chain reaction (ddPCR) and circulating epithelial cell (CEC) detection-as biomarkers for risk stratification in IPMN patients. We prospectively collected plasma samples from 25 resected patients at risk of malignant progression, and 23 under clinical surveillance. Our findings revealed KRAS mutations in 10.4% and GNAS mutations in 18.8% of the overall cohort. Among resected IPMN patients, KRAS and GNAS mutation detection rates were 16.0% and 32.0%, respectively, whereas both rates were 4.0% in conservatively managed IPMN. GNAS mutations in cfDNA were significantly more prevalent in resected IPMN (P = 0.024) compared with IPMN under surveillance. No CECs were detected. The absence of KRAS and GNAS mutations could be a reliable marker for branch duct IPMN without worrisome features. The emergence of GNAS mutations could prompt enhanced imaging surveillance. Neither the presence of established worrisome features nor GNAS or KRAS mutations appear effective in identifying high-grade dysplasia among IPMN patients.© 2024 The Author(s). Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.