TREC mediated oncogenesis in human immature T lymphoid malignancies preferentially involves ZFP36L2

Molecular Cancer

Correspondence

Bertrand Nadel¹  Dominique Payet-Bornet¹  André Baruchel²  Mélanie Feroul³  Elizabeth Macintyre³  Mathieu Simonin³  Estelle Balducci³  Agata Cieslak³  Vahid Asnafi³  Sophie Kaltenbach³  Marie-Emilie Dourthe³  Charlotte Smith³  Aurore Touzart³  Patrick Villarese³  Lucile Couronné³  Ludovic Lhermitte³  Thomas Steimlé⁴  Norbert Ifrah⁵  Nicolas Boissel⁶  Hervé Dombret⁶ 

[1] Aix Marseille Université, CNRS, INSERM, CIML, Marseille, France;Department of Pediatric Hematology and Immunology, University Hospital Robert Debré, Assistance Publique des Hôpitaux de Paris (APHP), Paris, France;Institut Universitaire d’Hématologie, EA-3518, University Hospital Saint-Louis, Assistance Publique des Hôpitaux de Paris (APHP), Paris, France;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;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;TAGC, UMR 1090, Aix-Marseille University, INSERM, Marseille, France;PRES LUNAM, CHU Angers Service Des Maladies du Sang, INSERM U 892, 49933, Angers, France;Université Paris Diderot, Institut Universitaire d’Hématologie, EA-3518, Assistance Publique-Hôpitaux de Paris, University Hospital Saint-Louis, 75010, Paris, France;

关键词: T-cell receptor excision circles (TREC);    Oncogenesis;    Cancer;   

DOI  :  10.1186/s12943-023-01794-y

 received in 2023-03-17, accepted in 2023-05-25,  发布年份 2023

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

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