Key Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan University, Guangzhou, 510632, P. R. China.
Department of Lymphoma, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, 510180, P. R. China.
Adv Biol (Weinh). 2023 Dec;7(12):e2300042. doi: 10.1002/adbi.202300042. Epub 2023 Sep 1.
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.
对原位肿瘤样本进行外显子组测序显示，突变基因可预测 T 细胞淋巴瘤（TCL）患者的预后。然而，源自循环肿瘤 DNA（ctDNA）的肿瘤突变负担（TMB）如何对 TCL 患者进行分层尚不清楚。
使用靶向外显子组测序分析了来自临床中心的 79 例新诊断 TCL 患者的血浆 ctDNA，并获得了来自癌症体细胞突变目录（COSMIC）数据库的 4035 例 TCL 患者的外显子组数据进行对比分析。
使用包含 120 个基因的panel（panel-TMB120）评估 TMB 较高的 TCL 患者，其预后不良。更重要的是，COX 回归分析确定了 panel-TMB120 中的 13 个基因亚组，包括 AP3B1（衔接蛋白复合物 3 亚基β 1）、ATM（共济失调毛细血管扩张突变）、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（鼠双微体 2）、NF1（神经纤维瘤 1）、STAT5B（信号转导和转录激活因子 5B）、STAT6（信号转导和转录激活因子 6）和 TET2（Tet 甲基胞嘧啶双加氧酶 2），这些基因与预后显著相关。具体来说，使用这 13 个基因（panel-TMB13）计算出的更高 TMB 值能够显著预测这些患者的不良预后。
综上所述，panel-TMB13 与国际预后指数（IPI）一起用于风险分层。鉴定出 panel-TMB13，其可以预测 panel-TMB13 评分较高的 TCL 患者的不良预后，并提示 panel-TMB13 可能是 TCL 患者补充风险分层的潜在生物标志物。
