Laboratory of Onco-Hematology, Necker Children's Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
Université Paris Cité, CNRS, INSERM U1151, Institut Necker Enfants Malades (INEM), Paris, France.
Mol Cancer. 2023 Jul 10;22(1):108. doi: 10.1186/s12943-023-01794-y.
The reintegration of excised signal joints resulting from human V(D)J recombination was described as a potent source of genomic instability in human lymphoid cancers. However, such molecular events have not been recurrently reported in clinical patient lymphoma/leukemia samples. Using a specifically designed NGS-capture pipeline, we here demonstrated the reintegration of T-cell receptor excision circles (TRECs) in 20/1533 (1.3%) patients with T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL). Remarkably, the reintegration of TREC recurrently targeted the tumor suppressor gene, ZFP36L2, in 17/20 samples. Thus, our data identified a new and hardly detectable mechanism of gene deregulation in lymphoid cancers providing new insights in human oncogenesis.
切除的人类 V(D)J 重组信号接头的重新整合被描述为人类淋巴癌中基因组不稳定性的一个重要来源。然而，在临床患者淋巴瘤/白血病样本中并没有反复报道此类分子事件。在这里，我们使用专门设计的 NGS 捕获管道，在 20/1533（1.3%）例 T 细胞急性淋巴细胞白血病（T-ALL）和 T 细胞淋巴母细胞淋巴瘤（T-LBL）患者中证实了 T 细胞受体切除环（TRECs）的重新整合。值得注意的是，TREC 的重新整合反复靶向肿瘤抑制基因 ZFP36L2，在 17/20 个样本中均有发现。因此，我们的数据确定了淋巴癌中基因失调的一种新的且难以检测到的机制，为人类肿瘤发生提供了新的见解。
