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

Published in: Molecular Cancer, 2023, 22 (1), pp.108. ⟨10.1186/s12943-023-01794-y⟩

Authors: Estelle Balducci, Thomas Steimlé, Charlotte Smith, Patrick Villarese, Mélanie Feroul, Dominique Payet-Bornet, Sophie Kaltenbach, Lucile Couronné, Ludovic Lhermitte, Aurore Touzart, Marie-Emilie Dourthe, Mathieu Simonin, André Baruchel, Hervé Dombret, Norbert Ifrah, Nicolas Boissel, Bertrand Nadel, Elizabeth Macintyre, Agata Cieslak, Vahid Asnafi

Summary

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.

Link to Pubmed [PMID] – 37430263

Link to HAL – hal-04237392

Link to DOI – 10.1186/s12943-023-01794-y