磷脂酰肌醇-3 激酶/AKT 通路突变的甲状腺癌预后较差。然而，关于组织学、突变谱和结果之间关系的知识仍在发展中。本研究评估了基因组图谱对接受常规治疗出现进展的晚期甲状腺癌患者的预后价值。对招募至国家临床肿瘤学项目的治疗难治性局部晚期、复发或转移性癌症的患者进行了分析。对患者的档案肿瘤样本进行了全面的基因组分析。特定致癌突变和癌症相关途径的存在与总体生存率相关。从 2018 年到 2021 年，招募了 4,955 名患者，其中 44 名患者（0.9%）诊断为甲状腺癌，其中 4 名髓质癌，其余滤泡来源癌：17 名分化型、 13 例低分化甲状腺癌和 10 例未分化甲状腺癌。在 40 个滤泡源性甲状腺癌样本中，17 个 (42.5%) 携带 TP53 突变，其次是 11 个 BRAF V600E (27.5%)、9 个 NRAS (22.5%)、9 个磷脂酰肌醇-3 激酶/AKT 通路突变(22.5%)，7 个有 TERT 启动子突变 (17.5%)。 TP53 和磷脂酰肌醇-3 激酶/AKT 通路改变均与总生存期降低相关（风险比，5.19；95% 置信区间，1.59-16.70，P = .02，风险比，10.12；95% 置信区间，1.61-63.76 ，P = .01)。 Cox 回归显示组织学类型为未变性甲状腺癌（风险比，12.93，P = .004）、低分化甲状腺癌（风险比，5.19，P = .039）以及 TP53 和/或磷脂酰肌醇-3 激酶/AKT 通路突变（风险比，4.73，P = .017）与总生存期独立相关。TP53 和/或磷脂酰肌醇-3 激酶/AKT 通路突变与晚期甲状腺癌患者的总生存期相关，与组织型无关。全面的基因组分析有可能为预后提供信息，并确定晚期甲状腺癌患者的治疗目标。版权所有 © 2024 Elsevier Inc. 保留所有权利。

Thyroid cancers with mutations in the phosphatidylinositol-3 kinase/AKT pathway have a poorer prognosis. However, knowledge about the relationship between histology, mutation profile, and outcomes is still developing. This study assessed the prognostic value of genomic profiles for patients with advanced thyroid cancer who experienced progression on conventional treatment.Patients recruited to a national clinical oncology program for treatment-refractory locally advanced, recurrent or metastatic cancers were analyzed. Patients' archival tumor samples underwent comprehensive genomic profiling. Specific oncogenic mutations and the presence of cancer related pathways were correlated with overall survival.From 2018 to 2021, 4,955 patients were recruited, with 44 (0.9%) having a diagnosis of thyroid cancer with 4 medullary and the remaining follicular derived: 17 differentiated, 13 poorly differentiated, and 10 anaplastic thyroid cancers. Of the 40 follicular-derived thyroid cancer samples, 17 (42.5%) carried TP53 mutations, followed by 11 with BRAF V600E (27.5%), 9 with NRAS (22.5%), 9 with mutations in the phosphatidylinositol-3 kinase/AKT pathway (22.5%), and 7 with TERT promoter mutations (17.5%). Both TP53 and phosphatidylinositol-3 kinase/AKT pathway alterations were associated with reduced overall survival (hazard ratio, 5.19; 95% confidence interval, 1.59-16.70, P = .02 and hazard ratio, 10.12; 95% confidence interval, 1.61-63.76, P = .01). Cox regression showed histologic type anaplastic thyroid cancer (hazard ratio, 12.93, P = .004), poorly differentiated thyroid cancer (hazard ratio, 5.19, P = .039), and TP53 and/or phosphatidylinositol-3 kinase/AKT pathway mutations (hazard ratio, 4.73, P = .017) were independently associated with overall survival.TP53 and/or phosphatidylinositol-3 kinase/AKT pathway mutations correlated with overall survival independently of histotype in patients with advanced thyroid cancer. Comprehensive genomic profiling has potential to inform prognosis, as well as identifying treatment targets for patients with advanced thyroid cancer.Copyright © 2024 Elsevier Inc. All rights reserved.