这份概念验证论文演示了在分化型甲状腺肿瘤中可以在血浆中检测到驱动突变，并且我们能够在高达80％的恶性甲状腺结节中检测到突变。此外，癌症亚型也可以使用8基因面板进行预测。在近90％的滤泡腺瘤中，可以检测到大鼠肉瘤病毒（RAS）突变。血浆样本、细针穿刺细胞学材料和组织病理样本中发现的驱动突变之间存在强烈的一致性。这具有潜力作为无创的、术前诊断工具（在不确定性结节中尤其具有临床价值），并可能有助于术后检测残留肿瘤。未来的研究有必要测试该工具在检测肿瘤复发方面的作用。超声检查和细针穿刺术（FNAC）是评估甲状腺肿瘤的基石。分子技术，包括从FNAC细胞学材料中检测驱动突变，是一种已经建立的模态。在本研究中，我们探讨了使用细胞外游离核酸检测已知驱动突变在分化型甲状腺肿瘤中的可行性。具有甲状腺结节的患者进行了超声检查，根据“甲状腺影像报告和数据系统”评分和FNAC（贝塞斯达分类）接受了治疗。所有贝塞斯达3、4、5、6级的患者接受了手术和组织病理学确认。贝塞斯达2级（美容问题、压迫症状）的患者接受了手术，其余人在超声、FNAC特征和临床随访的基础上被认为是良性的。内分泌诊所。患有甲状腺结节的受试者。无。对驱动突变（8基因面板，包括BRAF-V600E、RET/PTC3、RET/PTC1、TERT启动子、HRAS、NRAS、KRAS和PAX8-PPARG）进行了血浆样本、FNAC和组织病理材料的评估。招募了223名受试者，其中154名是良性的，69名患有分化型甲状腺癌。我们能够在所有恶性患者中的55名（79.71％）从血浆中检测到驱动突变，而在良性类别中有11名患者具有RAS突变（滤泡腺瘤）。其余良性结节没有检测到任何可检测的驱动突变。血浆可能是检测分化型甲状腺肿瘤患者的驱动突变（8基因面板）的可行无创替代来源，可能具有重要的临床应用价值。©2023年作者。由牛津大学出版社代表（ESE）欧洲内分泌学会出版。保留所有权利。请发送电子邮件至journals.permissions@oup.com以获得许可。

This proof-of-concept paper demonstrates that driver mutations can be detected in plasma in differentiated thyroid tumors, and we were able to detect mutations in upto 80% malignant thyroid nodules. Additionally, cancer subtypes could also be predicted using a 8-gene panel. In almost 90% follicular adenoma, rat sarcoma virus (RAS) mutations were detectable. There was a strong agreement between driver mutations found in plasma samples, FNAC materials, and histopathology samples. This has potential as a noninvasive, preoperative diagnostic tool (particularly of clinical importance in indeterminate nodules) and may help in detection of residual tumor after surgery. Future research is warranted to test the role of this tool to detect tumor recurrence.Ultrasonographic (USG) evaluation and fine-needle aspiration (FNA) are cornerstone for evaluation of thyroid neoplasm. Molecular technique including detection of driver mutation from FNA cytology (FNAC) material is an established modality. In this study, we explored the feasibility of using plasma cell-free nucleic acids to identify known driver mutations in differentiated thyroid neoplasm.Patients presenting with thyroid nodules underwent USG with Thyroid Image Reporting and Data Systems scoring and FNAC (Bethesda classification). All patients in Bethesda 3, 4, 5, 6 underwent surgery and histopathological confirmation. Patients in Bethesda 2 (cosmetic concerns, compressive symptoms) underwent surgery, and rest were presumed benign on the basis of USG, FNAC features, and clinical followup.).Endocrinology clinic.Subjects with thyroid nodule.None.Plasma sample, FNA, and histopathology material were evaluated for driver mutations (8-gene panel comprising BRAF-V600E, RET/PTC3, RET/PTC1, TERT promoter, HRAS, NRAS, KRAS, and PAX8-PPARG).A total of 223 subjects were recruited; of these 154 were benign and 69 had differentiated thyroid cancer. We were able to detect driver mutation from plasma in 55 subjects (79.71%) of all malignant patients, and 11 patients in benign category had RAS mutation (follicular adenoma). Rest of the benign nodules did not have any detectable driver mutations.Plasma might be a viable noninvasive alternative source for detection of driver mutations (8-gene panel) in subjects with differentiated thyroid tumors and may have significant clinical utility.© The Author(s) 2023. Published by Oxford University Press on behalf of (ESE) European Society of Endocrinology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.