原位肿瘤样本的外显子测序显示，突变基因可以预测T细胞淋巴瘤（TCL）患者的预后。然而，循环肿瘤DNA（ctDNA）所得的肿瘤突变负荷（TMB）如何对TCL患者进行分层尚不清楚。来自临床中心的79例新诊断的TCL患者的血浆ctDNA用于目标外显子测序，来自癌症中体细胞突变目录（COSMIC）数据库的4035例TCL患者的外显子数据用于比较分析。评估带有120个基因的面板（panel-TMB120）确定TMB较高的TCL患者与预后不良有关。更重要的是，COX回归分析在panel-TMB120中识别了13个基因子集，包括AP3B1（适配器相关蛋白复合物3亚单位β1）、ATM（遗传性血管扩张）、BCL6（B细胞淋巴瘤6）、BRAF（B-Raf原癌基因、丝氨酸/苏氨酸激酶）、CDKN2B（细胞周期蛋白依赖性激酶抑制剂2B）、EPCAM（上皮细胞黏附分子）、FBXO11（F-box蛋白11）、JAK1（Janus激酶1）、MDM2（Murine双分子2）、NF1（神经纤维瘤素1）、STAT5B（信号传导和转录激活因子5B）、STAT6（信号转导和转录激活因子6）和TET2（Tet甲基腺苷酸二氧化酶2），与预后显著相关。具体而言，这些13个基因计算得出的TMB较高（panel-TMB13）能够显著预测这些患者的不良预后。同时，panel-TMB13和国际预后指数（IPI）用于风险分层。我们确定了panel-TMB13，它可以预测携带较高panel-TMB13评分的TCL患者的不良预后，并且panel-TMB13可能是TCL患者辅助风险分层的潜在生物标志物。© 2023 Wiley-VCH GmbH.

Exome sequencing of in situ tumor samples reveals that mutated genes can predict the prognosis of patients with T-cell lymphoma (TCL). However, how tumor mutation burden (TMB) derived from circulating tumor DNA (ctDNA) may stratify TCL patients remains unclear.The plasma ctDNA of 79 newly diagnosed TCL patients from the clinical center is used for targeted exome sequencing, and the exome data of 4035 TCL patients from the Catalogue of Somatic Mutations in Cancer (COSMIC) database is obtained for comparison analysis.TCL patients with higher TMB, as evaluated with a panel of 120 genes (panel-TMB120), are associated with poor prognosis. More importantly, COX regression analysis identifies a subset of 13 genes in panel-TMB120, including AP3B1 (Adaptor related protein complex 3 subunit beta 1), ATM (Ataxia-telangiectasia mutated), BCL6 (B cell lymphoma 6), BRAF (B-Raf proto-oncogene, serine/threonine kinase), CDKN2B (Cyclin dependent kinase inhibitor 2B), EPCAM (Epithelial cell adhesion molecule), FBXO11 (F-box protein 11), JAK1 (Janus kinase 1), MDM2 (Murine double minute 2), NF1 (Neurofibromin 1), STAT5B (Signal transducer and activator of transcription 5B), STAT6 (Signal transducer and activator of transcription 6), and TET2 (Tet methylcytosine dioxygenase 2), which are significantly associated with prognosis. Specifically, higher TMB values calculated with these 13 genes (panel-TMB13) are able to significantly predict unfavorable prognosis for these patients. Together, panel-TMB13 and the International Prognostic Index (IPI) are used for risk stratification.Panel-TMB13 is identified, which can predict poor prognosis for TCL patients carrying higher panel-TMB13 scores and suggest that panel-TMB13 may be a potential biomarker for supplement risk stratification of TCL patients.© 2023 Wiley-VCH GmbH.