淋巴组织内毛细血管炎性T细胞淋巴瘤（AITL）患者的分子和临床分层方法不尽如人意，这妨碍了个体化治疗的发展。本研究旨在基于外周细胞游离DNA（cfDNA）鉴定AITL的分子生物标志物，以预测预后和指导非侵入性治疗。我们使用包含46个基因的自定义面板，对来自三个临床中心的64例中国AITL患者的术前cfDNA和相配的肿瘤组织进行研究，并对cfDNA和肿瘤组织中的基因突变进行一致性评估（34对样本）。然后，分析基因突变与预后的关联，并进行功能富集分析。测序结果显示cfDNA样本与配对的组织样本之间具有良好的一致性。我们鉴定了KDM5A、STAT1、FANCM、ERBB4、PIK3R5和NSD1作为新的经常性突变。FANCM的突变或RHOA、KDM5A和FAT1的组合与预后不良有关。此外，功能分析揭示了RHOAG17可能作为PD-1阻断治疗反应的预测生物标志物。我们的研究结果证实了cfDNA在AITL中作为液体活检的作用，并发现了可以分层患者和指导治疗选择的新的分子决定因素。© 2023英国血液学协会和John Wiley & Sons有限公司。

Molecular and clinical stratification of patients with angioimmunoblastic T-cell lymphoma (AITL) is unsatisfactory, which hinders the development of personalized therapies. This study aimed to identify molecular biomarkers for AITL based on peripheral cell-free DNA (cfDNA) that could be used to predict prognosis and guide treatment non-invasively. A customized panel containing 46 genes was used to study pretreatment cfDNA and paired tumour tissues in 64 Chinese AITL patients from three clinical centres, and gene mutations in cfDNA and tumour tissue were assessed for concordance (34 paired samples). Then, the association of gene mutations and prognosis was analysed, and a functional enrichment analysis was performed. The sequencing results showed good consistency between cfDNA samples and paired tissue samples. KDM5A, STAT1, FANCM, ERBB4, PIK3R5 and NSD1 were identified as novel recurrent mutations. Mutations in FANCM or combinations of RHOA, KDM5A and FAT1 were associated with poor prognosis. Additionally, functional analysis revealed that RHOAG17 might serve as a predictive biomarker of PD-1 blockade respondence. Our findings confirmed the role of cfDNA as a liquid biopsy in AITL, and revealed novel molecular determinants that can stratify patients and guide treatment options.© 2023 British Society for Haematology and John Wiley & Sons Ltd.